Intervent Neurol 2017;6:242–253

DOI: 10.1159/000477589 © 2017 S. Karger AG, Basel

Published online: August 17, 2017 www.karger.com/ine

Original Paper

Mechanical Thrombectomy for Middle

Cerebral Artery Division Occlusions:
A Systematic Review and Meta-Analysis
Hisham Salahuddin a Aixa Espinosa a Mark Buehler b Sadik A. Khuder c
Abdur R. Khan d Gretchen Tietjen a Syed Zaidi a Mouhammad A. Jumaa a
Departments of a Neurology, b Radiology and c Medicine and Public Health, University of
Toledo Medical Center, Toledo, OH, and d Cardiology Division, University of Louisville,
Louisville, KY, USA

Keywords
Stroke · Cerebrovascular accident · Infarction · Thrombectomy · M2 middle cerebral
artery occlusion · Middle cerebral artery division · Middle cerebral artery · Cerebrovascular
procedures · Cerebrovascular disease/stroke · Ischemic stroke

Abstract
Background: Middle cerebral artery division (M2) occlusion was significantly underrepresent-
ed in recent mechanical thrombectomy (MT) randomized controlled trials, and the approach
to this disease remains heterogeneous. Objective: To conduct a systematic review and meta-
analysis of outcomes at 90 days among patients undergoing MT for M2 middle cerebral artery
(MCA) occlusions. Methods: Five clinical databases were searched from inception through
September 2016. Observational studies reporting 90-day modified Rankin Scale scores for pa-
tients undergoing MT for M2 MCA occlusions with an M1 MCA control group were selected.
The primary outcome of interest was good clinical outcome 90 days after MT of an M1 or M2
MCA occlusion. Secondary outcomes of interest included mortality and excellent clinical out-
come, recanalization rates, significant intracerebral hemorrhage, and procedural complica-
tions. Results: A total of 323 publications were identified, and 237 potentially relevant articles
were screened. Six studies were included in the analysis (M1 = 1,203, M2 = 258; total n = 1,461).
We found no significant differences in good clinical outcomes (1.10 [95% CI, 0.83–1.44]), excel-
lent clinical outcomes (1.07 [0.65–1.79]), mortality at 3 months (0.85 [0.58–1.24]), recanalization
rates (1.06 [0.32–3.48]), and significant intracranial hemorrhage (1.19 [0.61–2.30]). Conclusions:
MT of M2 MCA occlusions is as safe as that of main trunk MCA occlusions, and comparable in
terms of clinical outcomes and hemorrhagic complications. Randomized clinical trials are
needed to assess the impact of MT in patients with M2 occlusions, given that M1 MCA occlu-
sions have different natural histories than M2 occlusions. © 2017 S. Karger AG, Basel

Mouhammad A. Jumaa, MD
Department of Neurology, University of Toledo Medical Center
Mail Stop 1195, 3000 Arlington Avenue
Toledo, OH 43614 (USA)
E-Mail mouhammad.jumaa @ utoledo.edu
 Intervent Neurol 2017;6:242–253 243
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Introduction

There is class IA evidence for treatment of acute stroke due to anterior circulation large
vessel occlusion with mechanical thrombectomy (MT), which is translated into the current
treatment guidelines [1]. Most of the studies conducted on MT in large vessel anterior circu-
lation strokes involved the internal carotid artery or main middle cerebral artery (MCA)
trunk (M1). The first division of the MCA (M2) segment is a common arterial occlusion site,
comprising about 20–41% [2] of anterior circulation strokes. Recanalization with intra-
venous tissue plasminogen activator (IV tPA) only occurs in about one-third of patients with
M2 occlusions [3], of which one-third may suffer from early reocclusion [4]. Occlusions in M2
vessels are more likely to be due to clots lodged in distal vessels [5] than due to large athero-
sclerotic plaques [6]. The smaller caliber of the vessels, thinner vessel walls, acute angles, and
increased tortuosity of distal vessels make MT of M2 vessels more challenging [7].
M2 occlusions have been significantly underrepresented in randomized studies conducted
until now [8–12]. This makes the role of MT in the management of M2 occlusions unclear. In
view of this uncertainty and the clinical and public health importance of M2 occlusions, we
conducted a systematic review and meta-analysis to evaluate the safety and efficacy of MT in
M2 occlusions.

Materials and Methods

Data Sources and Searches

The systematic review was carried out in accordance with the MOOSE (Meta-Analysis of Observational
Studies in Epidemiology) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
guidelines [13, 14] (see online supplement for the review protocol and suppl. Table IV for the PRISMA
checklist; for all online suppl. material, see www.karger.com/doi/10.1159/000477589).
On September 6, 2016, the search strategies and subsequent literature searches were performed by an
experienced health sciences reference librarian (Wade Lee). Search strategies which leveraged both
controlled vocabularies and keyword synonyms were developed for PubMed. This strategy was translated
to be used in Embase, the Cochrane Central Register of Controlled Trials, the Web of Science Core Collection
databases on the Thomson Reuters Web of Science platform, and ClinicalTrials.gov. The searches combined
the following concepts: thrombectomy/embolectomy and occlusion and the M2/secondary division of the
cerebral artery. Within the results for those combined concepts, additional filters, publication types, and
keyword strategies were used to identify and exclude the most common article types which did not report
trial results (see online supplement for an exemplary PubMed search). To identify further articles, references
were hand searched. All results were downloaded into EndNote (Thomson ISI ResearchSoft, Philadelphia,
PA, USA), a bibliographic database manager, and duplicate citations were identified and removed.

Study Selection
The abstracts of all studies were reviewed by two authors (H.S. and A.E.). Case reports, case series,
reviews, editorials, and unpublished data [15, 16] were excluded, limiting the results to clinical trials and
observational studies with an M1 MCA control group.
The primary outcome of interest was good clinical outcome at 90 days defined as a modified Rankin
Scale (mRS) score ≤2 after MT of an M1 or M2 MCA occlusion. Secondary outcomes of interest included
mortality and excellent clinical outcome at 90 days (defined as an mRS score ≤1), recanalization rates, symp-
tomatic intracerebral hemorrhage, and procedural complications.
Full texts of selected abstracts were obtained for review for inclusion into the study. Articles published
in languages other than English were excluded if no translation was available. Definition of the M2 segment
was taken as provided. Studies were excluded if they did not compare M2 occlusions to an M1 control group,
if they did not include separate measures of outcome for the respective groups, or if mRS scores at 90 days
for each group were not available.
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Data Extraction and Quality Assessment

Each study was evaluated for the following information: geographical location, inclusion and exclusion
criteria, study design, control groups, primary outcomes, MT device, MT cutoff times, imaging criteria used
for patient selection, patient baseline characteristics, baseline NIHSS score, Alberta Stroke Program Early CT
Scan (ASPECTS) score, treatment times, procedural complications, and clinical outcomes at 90 days. All
papers were independently reviewed and data extracted by two separate reviewers (H.S. and A.E.). In cases
of disagreement between the two reviewers, where a consensus could not be obtained, a third reviewer (M.J.)
was used.
Two reviewers (H.S. and A.E.) independently assessed the methodological quality of the selected studies
using the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies. This scale subjec-
tively assesses the selection of patients in each study, comparability of the patients within the two groups,
and the quality of assessment of primary outcomes and follow-up [17].

Data Synthesis and Statistical Analysis

For dichotomous variables, we computed an OR with 95% CI. Cochran’s Q test and the I2 statistic were
used to assess heterogeneity between studies [18]. We performed a fixed-effects analysis for studies with
minimal-to-no heterogeneity and a random-effects analysis for studies with moderate-to-substantial hetero-
geneity. A sensitivity analysis based on patient eligibility for IV tPA and the type of MT device used was
performed. Publication bias was assessed using a contour funnel plot and Egger’s test. The statistical analyses
were conducted using Review Manager version 5.3.5 and Comprehensive Meta-Analysis version 3.

Results

Study Selection and Characteristics

The librarian-performed search revealed 236 abstracts available for review from 5 online
databases after removal of duplicates. After reviewing the abstracts, 25 full-text papers were
reviewed for determination of the quality of fit. A total of 6 papers [19–24] were left from the
full-text review process after excluding abstracts, studies without the relevant outcome of
interest, analyses without control groups, or papers with overlapping data (Fig. 1).
Of the 6 included studies, 3 were post hoc analyses of pooled data from prospective
studies. Goyal et al. [21] evaluated patients from 5 recent randomized controlled trials [8, 10,
12, 25, 26], and Lemmens et al. [22] evaluated patients from the SWIFT [27], STAR [28],
DEFUSE 2 [29], and IMS III [30] studies. Shi et al. [24] evaluated clinical outcomes of secondary
division occlusions treated with MERCI stents from the MERCI [31] and Multi-MERCI trials
[32]. Studies containing overlapping data [33, 34] were selected based on the primary
endpoint evaluated and in order to include the largest data set.
Three other case-control studies [35–37] were excluded due to differences in duration
to assessment of clinical outcomes. The study by Protto et al. [38] was excluded as it examined
different endpoints based on the same data as from a study [23] by the same author used in
our analysis.
Three included case-control studies were performed after June 2010. Two of these
studies – those by Dorn et al. [19, 20] – included patients from Germany, one [20] of which
was a multicenter study from a stroke registry, and Protto et al. [23] looked at patients in
Finland. The 3 post hoc analyses [21, 22, 24] included data from multiple countries.
Online supplementary Table I summarizes the study characteristics of the 6 included
studies. The baseline characteristics are summarized in online supplementary Table II and
the treatment outcomes in online supplementary Table III.

Assessment of the Quality of the Included Studies

Assessment of bias was performed at the individual study level, and it revealed that the
included studies were of good methodological quality (online suppl. Table IV). There was
 Intervent Neurol 2017;6:242–253 245
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Color version available online

Records identified through
Identification database searching:
PubMed = 47
Embase = 155
Cochrane = 30 Additional records identified
Web of Science = 91 through other sources
(n = 323) (n = 1)

Records after duplicate removal

(n = 237)
Screening

Records excluded (n = 212):

Case reports and editorials = 16
Records screened Case series = 27
(n = 237) Different language = 1
Not related = 168

Full-text articles assessed Full-text articles excluded (n = 12):

for eligibility Duplicate = 1
Eligibility

(n = 25) Relevant outcome not available = 3

Studies included in Full-text articles excluded (n = 7):

qualitative synthesis Duration to outcome
(n = 13) assessment different = 3
Overlapping data = 2
Relevant outcome not available = 1
Inclusion of non-MT patients = 1
Included

Studies included in
quantitative synthesis
(meta-analysis)
(n = 6)

Fig. 1. PRISMA flow diagram.

excellent agreement between the reviewers for inclusion of studies, data extraction, and
quality assessment (κ = 1.0, 1.0, and 0.93, respectively).

Primary Analysis
This meta-analysis reviewed 6 studies on 1,203 patients with M1 occlusion and 258
patients with M2 occlusion. We found no significant differences in recanalization rates, signif-
icant intracranial hemorrhage, and clinical outcomes and mortality at 3 months between the
patients treated with endovascular therapy for M1 occlusion and those treated for M2
occlusion.
We constructed a fixed-effects model (minimal heterogeneity; I2 = 0%) for assessment of
good clinical outcomes (mRS score ≤2) at 3 months, mortality, and significant intracranial
hemorrhage. Good clinical outcomes at 90 days occurred in 534/1,191 (44.8%) of the patients
with M1 occlusions and in 121/257 (47.1%) of the patients with M2 occlusions, with a pooled
effect estimate of 1.10 (95% CI, 0.83–1.44). Excellent clinical outcomes occurred in a similar
proportion of patients in the M2 group (32.4%; 71/219) as in the M1 group (31.0%; 303/977),
 Intervent Neurol 2017;6:242–253 246
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Study or subgroup M2 M1 OR OR
events total events total weight, % M-H, fixed M-H, fixed
(95% CI) (95% CI)

1.5.1 MERCI devices

Lemmens, 2016 [22] 60 131 170 389 48.3 1.09 (0.73, 1.62)
Shi, 2010 [24] 11 27 46 138 9.3 1.38 (0.59, 3.20)
Subtotal 158 527 57.6 1.13 (0.79, 1.63)
Total events 71 216
Heterogeneity: χ2 = 0.24, df = 1 (p = 0.62); I2 = 0%
Test for overall effect: Z = 0.69 (p = 0.49)

1.5.2 Non-MERCI devices

Dorn, 2015 [19] 9 15 45 104 4.7 1.97 (0.65, 5.93)
Dorn, 2016 [20] 5 11 30 76 4.3 1.28 (0.36, 4.56)
Goyal, 2016 [21] 25 51 214 438 23.7 1.01 (0.56, 1.80)
Protto, 2016 [23] 11 22 29 46 9.8 0.59 (0.21, 1.64)
Subtotal 99 664 42.4 1.04 (0.68, 1.60)
Total events 50 318
Heterogeneity: χ2 = 2.59, df = 3 (p = 0.46); I2 = 0%
Test for overall effect: Z = 0.20 (p = 0.84)

Total 257 1,191 100.0 1.10 (0.83, 1.44)

Total events 121 534
Heterogeneity: χ2 = 2.92, df = 5 (p = 0.71); I2 = 0%
Test for overall effect: Z = 0.65 (p = 0.51) 0.1 0.2 0.5 1 2 5 10
a Test for subgroup differences: χ2 = 0.08, df = 1 (p = 0.77); I2 = 0% Favors M1 Favors M2

0.2
SE (log[OR])

0.4

0.6

0.8

1.0
0.1 0.2 0.5 1 2 5 10
b OR

Study or subgroup M2 M1 OR OR
events total events total weight, % M-H, random M-H, random
(95% CI) (95% CI)

Dorn, 2015 [19] 9 15 39 104 15.3 2.50 (0.83, 7.56)

Goyal, 2016 [21] 17 51 120 438 30.5 1.32 (0.71, 2.46)
Lemmens, 2016 [22] 40 131 125 389 39.9 0.93 (0.60, 1.42)
Protto, 2016 [23] 5 22 19 46 14.3 0.42 (0.13, 1.33)

Total 219 977 100.0 1.07 (0.65, 1.79)

Total events 71 303
Heterogeneity: τ2 = 0.12; χ2 = 5.66, df = 3 (p = 0.13); I2 = 47% 0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 0.27 (p = 0.78)
Favors M1 Favors M2
c
2
(Figure continued on next page.)
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Study or subgroup M2 M1 OR OR
events total events total weight, % M-H, fixed M-H, fixed
(95% CI) (95% CI)

4.3.1 MERCI devices

Lemmens, 2016 [22] 20 131 66 389 47.7 0.88 (0.51, 1.52)
Shi, 2010 [24] 7 27 48 146 18.8 0.71 (0.28, 1.81)
Subtotal 158 535 66.5 0.83 (0.52, 1.33)
Total events 27 114
Heterogeneity: χ2 = 0.15, df = 1 (p = 0.70); I2 = 0%
Test for overall effect: Z = 0.75 (p = 0.45)

4.3.2 Non-MERCI devices

Dorn, 2015 [19] 1 15 22 104 8.8 0.27 (0.03, 2.14)
Goyal, 2016 [21] 8 51 64 438 19.1 1.09 (0.49, 2.42)
Protto, 2016 [23] 3 22 6 46 5.7 1.05 (0.24, 4.67)
Subtotal 88 588 33.5 0.87 (0.45, 1.67)
Total events 12 92
Heterogeneity: χ2 = 1.61, df = 2 (p = 0.45); I2 = 0%
Test for overall effect: Z = 0.43 (p = 0.67)

Total 246 1,123 100.0 0.85 (0.58, 1.24)

Total events 39 206
Heterogeneity: χ2 = 1.79, df = 4 (p = 0.77); I2 = 0%
Test for overall effect: Z = 0.86 (p = 0.39) 0.05 0.2 1 5 20
d Test for subgroup differences: χ2 = 0.01, df = 1 (p = 0.93); I2 = 0% Mortality in M1 Mortality in M2

Fig. 2. Forest plots of good (mRS score ≤2) clinical outcomes (a), excellent (mRS score ≤1) clinical outcomes
(c), and mortality (d) at 90 days, and funnel plot showing the risk of publication bias in the included studies
(b). mRS, modified Rankin Scale.

and the results of the meta-analysis did not show a statistically significant difference (pooled
OR = 1.07; 95% CI, 0.65–1.79). Mortality did not differ either between the M1 group (18.3%;
206/1,123) and the M2 group (15.9%; 39/246), with a pooled effect estimate of 0.85 (95%
CI, 0.58–1.24) (Fig. 2).
The studies investigating successful recanalization had higher between-group heteroge-
neity (I2 = 78%) and similar rates of recanalization in both the M2 group (61.7%; 121/196)
and the M1 group (67.2%; 463/689), with a pooled effect estimate of 1.06 (95% CI, 0.32–
3.48). There were a total of 13 (6.6%) cases of significant intracranial hemorrhage among 196
cases of M2 thrombectomies and 39 (5.7%, n = 689) cases in the M1 group. There were no
significant differences between the groups in significant intracranial hemorrhage (1.19; 95%
CI, 0.61–2.30) and procedural complications (0.51, 95% CI, 0.09–2.79), although details
regarding procedural complications were lacking in most of the studies (Fig. 3b; online suppl.
Fig. I).
There was visual symmetry in the contour funnel plot (Fig. 2b). Egger’s test did not reveal
any evidence of publication bias.

Sensitivity Analysis
We performed a sensitivity analysis while evaluating clinical outcomes, mortality, recan-
alization rates, and symptomatic intracranial hemorrhage. A subgroup analysis evaluating
patients treated with second-generation MT devices only (excluding MERCI) and studies
evaluating patients eligible for IV tPA failed to reveal any significant differences in results
(online suppl. Table V; online suppl. Fig. II).
 Intervent Neurol 2017;6:242–253 248
DOI: 10.1159/000477589 © 2017 S. Karger AG, Basel
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Study or subgroup M2 M1 OR OR
events total events total weight, % M-H, random M-H, random
(95% CI) (95% CI)

5.2.1 MERCI recanalization

Lemmens, 2016 [22] 67 131 251 389 33.5 0.58 (0.39, 0.86)
Shi, 2010 [24] 23 28 90 150 27.7 3.07 (1.10, 8.51)
Subtotal 159 539 61.2 1.24 (0.24, 6.42)
Total events 90 341
Heterogeneity: τ2 = 1.26; χ2 = 9.04, df = 1 (p = 0.003); I2 = 89%
Test for overall effect: Z = 0.26 (p = 0.80)

5.2.2 Non-MERCI recanalization

Dorn, 2015 [19] 14 15 79 104 16.8 4.43 (0.55, 35.39)
Protto, 2016 [23] 17 22 43 46 22.0 0.24 (0.05, 1.10)
Subtotal 37 150 38.8 0.95 (0.05, 18.26)
Total events 31 122
Heterogeneity: τ2 = 3.71; χ2 = 5.27, df = 1 (p = 0.02); I2 = 81%
Test for overall effect: Z = 0.04 (p = 0.97)

Total 196 689 100.0 1.06 (0.32, 3.48)

Total events 121 463
Heterogeneity: τ2 = 1.05; χ2 = 14.14, df = 3 (p = 0.003); I2 = 79%
Test for overall effect: Z = 0.10 (p = 0.92) 0.05 0.2 1 5 20
a Test for subgroup differences: χ2 = 0.02, df = 1 (p = 0.87); I2 = 0% Favors M1 Favors M2

Study or subgroup M2 M1 OR OR
events total events total weight, % M-H, fixed M-H, fixed
(95% CI) (95% CI)

6.3.1 MERCI devices – significant ICH

Lemmens, 2016 [22] 9 131 20 389 60.2 1.36 (0.60, 3.07)
Shi, 2010 [24] 1 28 10 150 19.5 0.52 (0.06, 4.22)
Subtotal 159 539 79.6 1.16 (0.55, 2.44)
Total events 10 30
Heterogeneity: χ2 = 0.72, df = 1 (p = 0.40); I2 = 0%
Test for overall effect: Z = 0.38 (p = 0.70)

6.3.2 Non-MERCI devices – significant ICH

Dorn, 2015 [19] 1 15 6 104 9.1 1.17 (0.13, 10.42)
Protto, 2016 [23] 2 22 3 46 11.3 1.43 (0.22, 9.26)
Subtotal 37 150 20.4 1.31 (0.32, 5.40)
Total events 3 9
Heterogeneity: χ2 = 0.02, df = 1 (p = 0.89); I2 = 0%
Test for overall effect: Z = 0.38 (p = 0.70)

Total 196 689 100.0 1.19 (0.61, 2.30)

Total events 13 39
Heterogeneity: χ2 = 0.75, df = 3 (p = 0.86); I2 = 0%
Test for overall effect: Z = 0.51 (p = 0.61) 0.05 0.2 1 5 20
b Test for subgroup differences: χ2 = 0.03, df = 1 (p = 0.87); I2 = 0% ICH in M1 ICH in M2

Fig. 3. Forest plots of recanalization rates (a) and rates of significant intracranial hemorrhage (ICH) (b).

Discussion

Our meta-analysis comparing patients with secondary MCA branch occlusions (n = 258)
to those with main MCA occlusions (n = 1,203) revealed similar rates of recanalization, signif-
icant intracranial hemorrhage, and clinical outcomes. The present work is the largest and
most current meta-analysis of MT in patients with M2 MCA occlusions.
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Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

The duration to endovascular treatment varied between the studied populations. Three
[21, 22, 24] of the 6 analyzed studies mentioned varying cutoff times to MT. These studies
included patients from the MR CLEAN [9] (cutoff time 6 h), STAR [28] (8 h), ESCAPE [10], and
DEFUSE 2 [29] (each 12 h) trials. The 3 other studies [19, 20, 23] did not specify a cutoff time
used for MT. There were inconsistencies in reporting of door-to-recanalization times between
the studies, with 3 studies reporting mean times [19, 20, 23], 1 study reporting median times
[21], and 2 studies not providing any time to recanalization [22, 24]. The patients from the
MERCI and Multi MERCI studies had significantly longer procedure times, possibly due to
different endovascular techniques, less experience, and use of first-generation stent retrievers
in these earlier studies.
The median ASPECT score was comparable across all studies in both groups. The selection
of patients was based on similar modalities (CT or MR angiogram) across the recently
performed studies [20, 21, 23]. In patients who did not undergo noninvasive vessel imaging,
confirmation of the occlusion was made by digital subtraction angiography. Dorn et al. [19]
did not specify the imaging modality used, and the study by Lemmens et al. [22] included IMS
III [30] trial patients only if there was digital subtraction angiography evidence of intracranial
occlusions. The imaging selection criteria likely did not have a significant effect on our results,
given that classifications of stroke occlusion were confirmed retrospectively.
The rates of tPA administration also varied between the studies, ranging from 14 to 74%.
Dorn et al. [20] evaluated large vessel occlusion in patients who were ineligible for tPA, and
they found similar clinical outcomes and overall rates of intracranial hemorrhage.
The Solitaire FR thrombectomy device was the most commonly used device, followed by
MERCI and Trevo, but other stents including ERIC [23], CAPTURE [23], REVIVE [23], and
PRESET [20] were also used. Dippel et al. [39] found no evidence for a differential effect based
on the type of stent used when assessing 233 patients with Trevo or Solitaire stents from the
MR CLEAN trial [9]. The SWIFT trial [27] clearly demonstrated a superiority of the Solitaire
device over first-generation MERCI devices, and thus inclusion of these stents, albeit few
could affect rates of recanalization and clinical outcome. Thrombectomy with MERCI devices
was performed in the MERCI [31] and Multi MERCI [32] trials included in the analysis by Shi
et al. [24] as well as in the IMS III [30], SWIFT [27], and DEFUSE 2 trials included in the
analysis by Lemmens et al. [22]. The sensitivity analysis excluding studies [22, 24] using these
devices did not affect our results. Technical considerations such as vessel diameter and tortu-
osity, risk of embolization downstream or to unaffected territory, and clot resistance may
favor one device over the other and should be studied in a prospective manner.
Rates of recanalization were measured by TICI (thrombolysis in cerebral infarction)
2b–3 recanalization, with the exception of patients from the MERCI [31], Multi MERCI [32],
and SWIFT [27] trials, in which recanalization was classified by TIMI (thrombolysis in
myocardial infarction) score. The increased heterogeneity in recanalization rates may be
related to differing cutoff times for MT, use of different devices and center protocols, and
varying user experiences.
We analyzed the rates of symptomatic intracranial hemorrhage across the included
studies. We found no significant differences in intracranial hemorrhage between the two
groups after adjusting for type of stent used and type of study performed. There was signif-
icant heterogeneity in the definition of symptomatic intracranial hemorrhage, with some
studies not clearly defining symptomatic intracranial hemorrhage, while others used the
ECASS or SITS MOST criteria; therefore, we used the term “significant intracranial hemor-
rhage” in our study.
Procedural complications were not uniformly evaluated across the studies. Only 2 studies
reported procedural complications for each group, both of which revealed lower compli-
cation rates in the M2 MCA group (OR = 0.74; 95% CI, 0.13–4.18).
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Occlusions: A Systematic Review and Meta-Analysis

Current data on the natural history of M2 MCA occlusions are relatively sparse. An
analysis of untreated patients with proximal intracranial arterial occlusions by Lima et al.
[40] found a 46% rate of poor clinical outcomes amongst patients with M2 MCA occlusions
(n = 48) and found no association between intracranial arterial occlusion level (i.e., internal
carotid artery vs. M1 vs. M2) and clinical outcome. The largest cohort used for evaluating M2
occlusions was in a multicenter retrospective study [41] with pooled data from 10 US centers.
This study also revealed that MT is reasonable, safe, and effective for treatment of M2 MCA
occlusions.

Limitations
Our study has multiple limitations. The results of our analysis are weakened by limita-
tions inherent in the meta-analysis and the limitations of the included studies. The small
number of studies included in our analysis increases the risk of confounding. The studies
included patients with similar baseline characteristics, although some studies were not
powered or designed to detect differences in clinical outcomes between M1 and M2 MCA
occlusions. The most severe limitation of this study is the lack of an adequate control group,
given that studies comparing clinical outcomes in patients undergoing MT for M2 occlusions
and the natural history of the disease were largely lacking. By using patients undergoing MT
for M1 occlusion, we compared the outcomes to those of patients undergoing MT for currently
approved indications, albeit for a different disease. Another potential limitation is the possi-
bility of misclassification bias, since most of the studies did not clearly define the M2 MCA
region. Furthermore, our study evaluated a heterogeneous group of studies performed over
a long period of time; the inclusion of patients from the older MERCI [31] and Multi MERCI
[32] trials may have resulted in the loss of a treatment effect with new-generation stents.
Additionally, varying definitions of symptomatic intracranial hemorrhage were used across
the evaluated studies. Additionally, it is conceivable that this comparison may not be bene-
ficial, given the differences in natural history [42] and response to IV tPA [3] between the two
groups. Lastly, our analysis included studies in which patients were not randomized to
treatment, likely resulting in the selection of only the most severely affected M2 occlusion
patients for MT.
Our findings are consistent with those of previous studies, including recent retrospective
cohorts [41] and a pooled analysis of 5 randomized controlled trials [21]. Inconsistencies in
defining the M2 MCA branch, evaluating treatment times, defining symptomatic intracranial
hemorrhage, and describing procedural complications are the main limitations of our analysis.
A selection bias while evaluating patients with M2 MCA occlusions remains the largest
obstacle to an adoption of aggressive approaches for this disease; data from the Trevo, Soli-
taire, and HERMES registries may help provide further evidence on M2 occlusions.

Conclusion

MT for M2 MCA occlusions appears to be as safe and effective as MT for main trunk MCA
occlusions, with comparable clinical outcomes and hemorrhagic complications. Future
randomized controlled trials are warranted.

Acknowledgements

Thanks are due to Wade Lee and Faraz Khan Luni, MD.
 Intervent Neurol 2017;6:242–253 251
DOI: 10.1159/000477589 © 2017 S. Karger AG, Basel
www.karger.com/ine
Salahuddin et al.: Mechanical Thrombectomy for Middle Cerebral Artery Division
Occlusions: A Systematic Review and Meta-Analysis

Disclosure Statement

The authors have no conflicts of interest to disclose. This study received no external funding.

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