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ORIGINAL RESEARCH
CTA collateral score predicts infarct volume and
clinical outcome after endovascular therapy for
acute ischemic stroke: a retrospective chart review
Lucas Elijovich,
1,2,3
Nitin Goyal,
1
Shraddha Mainali,
4
Dan Hoit,
2,3
Adam S Arthur,
2,3
Matthew Whitehead,
5
Asim F Choudhri
6
1
Department of Neurology,
University of Tennessee Health
Sciences Center, Memphis,
Tennessee, USA
2
Department of Neurosurgery,
University of Tennessee Health
Sciences Center, Memphis,
Tennessee, USA
3
Semmes-Murphey Neurologic
and Spine Institute, Memphis,
Tennessee, USA
4
Department of Neurology,
University of Texas
Southwestern, Dallas, Texas,
USA
5
Department of Radiology,
George Washington University,
Washington DC, USA
6
Department of Radiology,
University of Tennessee Health
Sciences Center, Memphis,
Tennessee, USA
Correspondence to
Dr Lucas Elijovich, Department
of Neurosurgery, University of
Tennessee Health Sciences
Center, Semmes-Murphey
Neurologic and Spine Institute,
6325 Humphreys Blvd,
Memphis, TN 38120, USA;
lelijovich@semmes-murphey.
com
Received 10 March 2015
Revised 21 April 2015
Accepted 28 April 2015
To cite: Elijovich L,
Goyal N, Mainali S, et al.
J NeuroIntervent Surg
Published Online First:
[please include Day Month
Year] doi:10.1136/
neurintsurg-2015-011731
ABSTRACT
Background Acute ischemic stroke (AIS) due to
emergent large-vessel occlusion (ELVO) has a poor
prognosis.
Objective To examine the hypothesis that a better
collateral score on pretreatment CT angiography (CTA)
would correlate with a smaller final infarct volume and a
more favorable clinical outcome after endovascular
therapy (EVT).
Methods A retrospective chart review of the University
of Tennessee AIS database from February 2011 to
February 2013 was conducted. All patients with
CTA-proven LVO treated with EVT were included.
Recanalization after EVT was defined by Thrombolysis in
Cerebral Infarction (TICI) score ≥2. Favorable outcome
was assessed as a modified Rankin Score ≤3.
Results Fifty patients with ELVO were studied. The
mean National Institutes of Health Stroke Scale score
was 17 (2–27) and 38 of the patients (76%) received
intravenous tissue plasminogen activator. The
recanalization rate for EVT was 86.6%. Good clinical
outcome was achieved in 32% of patients. Univariate
predictors of good outcome included good collateral
scores (CS) on presenting CTA (p=0.043) and successful
recanalization (p=0.02). Multivariate analysis confirmed
both good CS (p=0.024) and successful recanalization
(p=0.009) as predictors of favorable outcome. Applying
results of the multivariate analysis to our cohort we were
able to determine the likelihood of good clinical
outcome as well as predictors of smaller final infarct
volume after successful recanalization.
Conclusions Good CS predict smaller infarct volumes
and better clinical outcome in patients recanalized with
EVT. These data support the use of this technique in
selecting patients for EVT. Poor CS should be considered
as an exclusion criterion for EVT as patients with poor
CS have poor clinical outcomes despite recanalization.
INTRODUCTION
Acute ischemic stroke (AIS) due to emergent large-
vessel occlusion (ELVO) in the intracranial circula-
tion has a poor natural history and results in high
morbidity and mortality without successful revascu-
larization.
1
Treatment of AIS with intravenous
tissue plasminogen activator (IV tPA) has been
shown to improve outcome, yet there is a low
rate of recanalization in patients with LVO.
2
Endovascular treatment (EVT) with the newest gen-
eration of stent-retrieval devices has resulted in sig-
nificantly higher rates of recanalization.
34
Recent
randomized clinical trials have shown that the
higher recanalization rates achieved with EVT com-
pared with IV tPA result in better outcomes with
the former.
15–9
However, the rate of good out-
comes varied widely in these clinical trials from
32.6 to 71.0%.
189
Studies suggest that the volume of core infarct at
presentation observed by diffusion-weighted
imaging is the strongest and most reliable predictor
of outcome and response to IV tPA and EVT.
10–12
The size of the final infarct and growth of the pen-
umbra are also influenced by the extent of lepto-
meningeal collaterals.
13
CT angiography (CTA) can
be used to identify collaterals and has also been
shown to predict outcome in patients who receive
IV tPA and may improve the degree of recanaliza-
tion with EVT.
14
We hypothesized that patients with good lepto-
meningeal collaterals seen on CTA would have
smaller infarct volumes and better clinical outcome
after successful mechanical revascularization.
METHODS
This study is a retrospective chart review of the
University of Tennessee Health Science Center
acute ischemic stroke database from February 2011
to February 2013, including consecutive patients
who underwent EVT for the treatment of AIS due
to LVO. The major inclusion criteria were the pres-
ence of LVO on pretreatment CTA and age
>18 years. Baseline characteristics were gathered,
including details of treatment, and determination
of clinical outcome.
CT and CTA were performed on a 64-slice
scanner. CT slice thickness was 1.25 mm with
acquisitions in axial, sagittal, and coronal planes
with 3D reformations. All diagnostic imaging was
independently interpreted by two blinded neurora-
diologists (MW, AFC). The CTA site of arterial
occlusion and the CTA collateral scores (CS) were
recorded. CS for the anterior circulation were
reported in a dichotomized fashion (ie, poor vs
good) using a methodology that has been shown to
predict clinical outcome in the setting of IV tPA.
This technique uses standard injection rates and
acquisition parameters for CTA of the head and
neck that are obtained identically to those for
imaging the craniocerebral vasculature in the
setting of AIS (figure 1).
14
Patients with vertebroba-
silar occlusion were assigned a good collateral
score, if two posterior communicating arteries were
Elijovich L, et al.J NeuroIntervent Surg 2015;0:1–4. doi:10.1136/neurintsurg-2015-011731 1
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seen on the CTA and the occlusion did not involve the top of
the basilar artery. The neuroradiologists also calculated the final
infarct volume using the ABC/2 method of volume calculation
based on 12–24 h MRI, diffusion-weighted imaging, or last
follow-up CT, if MRI was not available.
15
According to the
institutional protocol, the site of arterial occlusion, angiographic
collateral score (ie, the Acute Stroke Therapy by Inhibition of
Neutrophils—or ASTIN—method), and degree of recanalization
(ie, the Thrombolysis in Cerebral Infarction—or TICI—score)
were recorded prospectively in the stroke database at the time
of treatment by the interventional team.
16
The primary clinical outcome was the modified Rankin scale
(mRS) score at discharge. According to institutional protocol
the mRS was reported prospectively on the physical therapy
progress notes and abstracted by the investigators. A mRS of ≤3
was considered a favorable outcome at discharge. Final infarct
volume was recorded as a secondary outcome.
Univariate predictors of outcome were determined with χ
2
and Student t tests. Stepwise multivariate regression analysis
(MVR) was performed to determine predictors of outcome. The
results of our MVR analysis were then used to estimate the like-
lihood of a good clinical outcome based on the individual
characteristics of the patient’s clinical situation and treatment
course. Statistical analysis was performed using STATA SE/13.0
software (College Station, Texas, USA).
Because our study was a retrospective study using data from a
prospective clinical stroke registry, the grading of clinical out-
comes and the degree of recanalization were not blinded, which
might have led to selection bias. We attempted to address this
by blinding the neuroradiologists—who were not involved in
the care of the patients—when they determined the CS and
final infarct volume.
Institutional investigation review board approval for this
study was granted based on the prospectively maintained
University of Tennessee Health Sciences Center acute ischemic
stroke database (10-01003-XP).
RESULTS
A total of 50 patients who met the inclusion criteria were
treated during the study period. The mean patient age was
64.6 years and the mean National Institutes of Health Stroke
Scale (NIHSS) score was 17 (range 2–27). The majority of
patients were treated with IV tPA (76.0%) and with third-
generation thrombectomy devices (90%), defined as a stentrie-
ver and/or direct aspiration via a large-bore (≥5 Fr) intracranial
reperfusion catheter. The most common sites of arterial occlu-
sion were the middle cerebral artery (M1) (50%), middle cere-
bral artery (M2) (10%), internal carotid artery (30%), and
basilar artery 5 (10%). Good CS were observed in 38/50 (76%)
patients. A comparison of patients with good CS and those with
poor CS showed no significant differences in their baseline
characteristics (table 1). The overall rate of TICI ≥2 recanaliza-
tion was 86.6%.
Univariate analysis showed that successful recanalization
(p=0.02) and the presence of a good CS ( p=0.043) both pre-
dicted favorable discharge outcome. There was a lower final
Figure 1 CT angiography (CTA) collateral score (CS). (A) CTA image from a patient in late 50s with a right middle cerebral artery (MCA) M1
occlusion with no vascular markings apparent in the entire occluded MCA territory consistent with CS of 0. (B) Patient in early 80s with right MCA
M1 occlusion with vascular markings apparent in <50% but >0% of the occluded MCA territory consistent with CS of 1. (C) Patient in mid-50s with
a left MCA M1 occlusion with collaterals in >50% but <100% of the occluded MCA territory consistent with CS of 2. (D) Patient in late 70s with a
right MCA M1 occlusion with almost complete reconstitution of the entire MCA territory (100%) consistent with CS of 3. For the purpose of study,
collaterals were reported in a dichotomized fashion—poor (CS=0) versus good (CS=1, 2, and 3). (E). Patient in mid-to-late 60s with basilar
occlusion, good collaterals, and two large posterior communicating arteries. (F) Patient in mid-60s with basilar occlusion and poor posterior
circulation collaterals with one small posterior communicating artery visualized on the left (black arrow).
2 Elijovich L, et al.J NeuroIntervent Surg 2015;0:1–4. doi:10.1136/neurintsurg-2015-011731
Ischemic stroke
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infarct volume in patients who had good collaterals (106 vs
174.4 ml, p=0.08). Multivariate analysis showed good CS
(p=0.024) and successful recanalization (p=0.009) to be pre-
dictors of favorable outcome. Additional multivariate analysis of
the final infarct volume emphasized the importance of collat-
erals in patients who had revascularization, demonstrating a sig-
nificantly lower final infarct volume in the group with good CS
(p=0.001). Patients with higher systolic blood pressure on pres-
entation had significantly higher final infarct volumes despite
successful revascularization (p<0.0001). The predictors of good
outcome from the multivariate analysis and the use of IV tPA
were then used to predict the likelihood of a good outcome.
The highest percentage of good clinical outcomes (52.7%) was
seen when a patient was treated with IV tPA, had good CS, and
successful recanalization. The absence of one of these three
favorable clinical characteristics progressively reduced the rate
of good outcome, with a good clinical outcome of only 2.0%
seen in patients who had recanalization with poor CS and
without IV tPA administration (figure 2).
DISCUSSION
This study shows that a good CS predicts both a favorable clin-
ical response and decreased final infarct volume in patients with
ELVO treated with mechanical embolectomy. The best imaging
selection strategy for patients with ELVO remains unresolved
with contradictory results that expose the limitations of CT and
MR perfusion. Results of the DEFUSE 2 prospective registry
suggested that MRI perfusion (MRP) could be used to predict
favorable response to EVT, with good outcome in patients with
a favorable ‘target mismatch’MRP profile.
12
However, a similar
MRP protocol in MR RESCUE, a randomized clinical trial,
failed to corroborate this hypothesis.
6
The MR CLEAN trial did
demonstrate the superiority of EVT compared with IV thromb-
olysis alone; however, only 32.6% of patients achieved a favor-
able clinical outcome.
1
There was no prespecified multimodal
imaging patient selection criteria in the trial, therefore it is
encouraging to see that both ESCAPE and EXTEND-IA did
have higher rates of good outcomes (53% and 71% mRS 0–2)
than MR CLEAN using CTA collaterals and perfusion CT to
select patients.
89
Although our study was not a randomized
controlled trial, it does provide unique information about collat-
erals compared with ESCAPE and other trials using multimodal
imaging selection because our cohort of patients were all
treated. Therefore, information about outcomes in patients with
unfavorable imaging profiles as determined by CS can be
evaluated.
The result from the predictive model in our study shows that
patients with poor CS have only 2% good outcomes despite
revascularization. Owing to the high cost and potential risk of
these procedures, identifying this subgroup is as important as
finding salvageable patients. Furthermore, revascularization of
patients with poor CS may result in significant harm with
higher infarct volume, increased malignant brain edema, and
higher rates of intracerebral hemorrhage as seen in MRI
studies.
17
We could not draw any conclusions about this owing
to the small number of patients in our study. Additionally, the
low rate of symptomatic intracerebral hemorrhage (2.0%) and
improved outcomes in patients receiving IV tPA adds further
data to support the safety and efficacy of bridging therapy, par-
ticularly in the group of patients with good CS. The multivari-
ate analysis also showed that patients with higher presenting
systolic blood pressure fared worse despite good CS. This
Table 1 Baseline characteristics of patients with good collateral
score versus poor collateral scores
Characteristics
Patients with
good collateral
score (n=38)
Patients with
poor collateral
score (n=12) p Value
Age, mean (range) 64 (38–86) 64 (33–83) 0.81
Hypertension, % 84 91.6 0.51
Hyperlipidemia, % 66 58 0.63
Diabetes, % 47 58 0.41
Atrial fibrillation, % 29 25 0.79
IV tPA treated, % 76 67 0.50
NIHSS, mean (range) 17 (2–27) 16 (12–23) 0.52
Door to needle IV tPA (min),
mean
57.8 72.5 0.10
Onset to arterial puncture
(min), mean
268 282 0.71
Onset to revascularization
(min), mean
348 392 0.32
IV tPA, intravenous tissue plasminogen activator; NIHSS, National Institutes of Health
Stroke Scale.
Figure 2 Rates of good clinical
outcome as determined by collateral
score, recanalization, and intravenous
tissue plasminogen activator (IV tPA)
administration.
Elijovich L, et al.J NeuroIntervent Surg 2015;0:1–4. doi:10.1136/neurintsurg-2015-011731 3
Ischemic stroke
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significance of this finding is unclear, but it may suggest that
these patients are unhealthier or that acutely raised systolic
blood pressure is a marker of a large volume infarction or
intense ischemia.
A recent study by Nambiar et al
18
showed similar results with
statistically significant improved outcome (70% mRS ≤2at
90 days) in patients with EVT with intermediate to good CTA
collaterals based on the regional leptomeningeal collateral score
from pretreatment CTA. The higher rates of good outcome
reported by Nambiar et al may be attributed to several factors,
including 90-day outcomes, differences in the definition of suc-
cessful recanalization (TICI ≥2 in our study and TICI ≥2b in
the study of Nambiar et al), the inclusion of patients with
basilar occlusion in our study, and the overall higher presenting
NIHSS in our cohort (ie, 17 vs 14). Despite these differences,
the similar results reinforce the importance of collateral status as
a potential patient selection tool.
This study has several important limitations. As mentioned
above, this was a retrospective study using data from a prospect-
ive clinical stroke registry. Therefore, the grading of clinical out-
comes and the degree of recanalization was not blinded. In
contrast, the CS and final infarct volume determinations were
obtained by blinded neuroradiologists who were not involved in
the care of the patients. The final infarct volume was not evalu-
ated on the same day of illness in all patients, and some patients
received follow-up imaging with MRI and others with CT.
Additionally, infarct volume data were not available for all
patients as routine imaging was not mandated. We believe this
might have led to an overestimation of final infarct volumes
given the propensity to image sicker patients who did not fail to
recanalize or who did not have clinical improvement after
recanalization.
Rapid and reproducible imaging is essential to modern AIS
care. This study adds to the growing body of reports that sup-
ports the use of CTA collaterals independent of perfusion
imaging as a rapid and accurate method assisting in patient
selection for EVT.
Twitter Follow Asim Choudhri at @AsimChoudhriMD
Acknowledgements The authors thank Andrew J Gienapp (Department of
Medical Education, Methodist University Hospital, Memphis, Tennessee and
Department of Neurosurgery, University of Tennessee Health Science Center,
Memphis, Tennessee) for technical and copy editing, preparation of the manuscript
and figures for publishing, and publication assistance with this manuscript.
Contributors All authors of this work met International Committee of Medical
Journal Editors criteria for authorship and made substantial contributions to the
conception and design, acquisition of data, analysis and interpretation of data,
drafting, critical revision, and final approval of this manuscript.
Competing interests LE has served as a consultant for Stryker Neurovascular,
Microvention, and Codman Neurovascular. DH has served as a consultant for
Covidien. ASA served as a consultant for Covidien, Johnson and Johnson, Siemens,
Stryker, and Terumo; and received grants from Siemens and Terumo.
Ethics approval University of Tennessee Health Sciences Center acute ischemic
stroke database (10-01003-XP).
Provenance and peer review Not commissioned; externally peer reviewed.
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4 Elijovich L, et al.J NeuroIntervent Surg 2015;0:1–4. doi:10.1136/neurintsurg-2015-011731
Ischemic stroke
group.bmj.com on May 31, 2015 - Published by http://jnis.bmj.com/Downloaded from
retrospective chart review
therapy for acute ischemic stroke: a
and clinical outcome after endovascular
CTA collateral score predicts infarct volume
Matthew Whitehead and Asim F Choudhri
Lucas Elijovich, Nitin Goyal, Shraddha Mainali, Dan Hoit, Adam S Arthur,
published online May 20, 2015J NeuroIntervent Surg
1
http://jnis.bmj.com/content/early/2015/05/20/neurintsurg-2015-01173
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