American Journal of Neuroradiology 27:1528-1531, August 2006
© 2006 American Society of Neuroradiology
INTERVENTIONAL
Arteriographic Demonstration of Slow Antegrade Opacification Distal to a Cerebrovascular Thromboembolic Occlusion Site As a Favorable Indicator for Intra-Arterial Thrombolysis
G.A. Christoforidisa,
Y. Mohammadb,
B. Avutua,
A. Tejadaa and
A.P. Slivkab
a Department of Radiology, The Ohio State University Medical Center, Columbus, Ohio
b Department of Neurology, The Ohio State University Medical Center, Columbus, Ohio
Address correspondence to Gregory A. Christoforidis, 627 Means Hall, 1654 Upham Dr, Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210; e-mail: greg.christoforidis{at}osumc.edu
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Abstract
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PURPOSE: This study sought to determine whether the angiographic
demonstration of slow antegrade contrast opacification of an
occluded cerebral artery distal to the thrombus (clot outline
sign) on cerebral arteriograms performed immediately before
thrombolytic treatment is associated with higher recanalization
rates relative to patients without antegrade contrast opacification
distal to the occlusion site.
METHODS: The angiographic images of 100 consecutive arteriograms performed before thrombolysis in patients eligible for intra-arterial thrombolysis from May 1995 to February 2005 were reviewed. A modified Thrombolysis in Myocardial Infarction flow grade (mTIMI) was adapted to grade recanalization after cerebral thrombolysis. Clot outline sign was defined as slow antegrade contrast opacification distal to the thrombus on the delayed images of the presenting arteriogram. Logistic regression analysis for mTIMI grade included the following potential predictors: presence of outline sign, age, time to treatment, sex, site of occlusion, presenting National Institutes of Health Stroke Scale (NIHSS) score, presenting platelets, presenting systolic blood pressure, presence of pial collaterals, and admitting glucose value.
RESULTS: Eighty-seven arteriograms were reviewed. Of these, 19 (22%) displayed the clot outline sign. Thirteen (69%) of 19 had clot outline sign, and 16 of 68 (29%) were not completely recanalized (mTIMI = 3); 95% with clot outline sign and 54% without were associated with either mTIMI 2 or 3 (P = .0055, Pearson correlation). Logistic regression analysis for recanalization relative to other predictors indicates that only the clot outline sign could act as a statistically significant predictor for recanalization (P = .0007).
CONCLUSION: Prethrombolysis cerebral arteriograms demonstrating delayed antegrade contrast opacification distal to the occlusion site are associated with higher recanalization rates.
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Introduction
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Recanalization of occluded intracranial vessels after intra-arterial
thrombolytic treatment delivered within 6 hours after symptom
onset in acute ischemic stroke has been shown to improve outcomes
and reduce infarct volumes.
1–3 Complete recanalization
rates, however, vary between studies involving patients undergoing
intra-arterial thrombolysis for acute ischemic stroke.
1–5 Few factors associated with successful recanalization have been
reported. Site of occlusion and angiographic appearance have
been shown to be associated with differing recanalization rates.
5–7 This investigation sought to determine whether the objective
angiographic finding of slow antegrade contrast opacification
of an occluded cerebral artery distal to thrombus (clot outline
sign) on cerebral arteriograms immediately before intra-arterial
thrombolytic treatment is associated with higher recanalization
rates.
The clot outline sign is similar to what is defined as Thrombolysis in Myocardial Infarction (TIMI) grade 1 (penetration of contrast distal to the occlusion site). Morphologic descriptions of the occlusion site as "tram track appearance" or "tapered" have been associated with higher recanalization rates.7 This type of description, however, is somewhat subjective. Identification of the contrast distal to the occlusion site depends on a single finding and would be expected to be more objective and more reproducible than a morphologic description as "tram track" or "tapered," which introduces an element of subjectivity.
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Materials and Methods
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This study retrospectively reviewed the records and available
images from 100 consecutive arteriograms performed before thrombolysis
in patients eligible for intra-arterial thrombolysis. Patients
were excluded if the arteriogram was not available for review,
if the operator purposefully occluded the parent vessel (ie,
treated parent vessel perforation), or the microcatheter was
not able to reach the occlusion site. Patients in whom balloon
angioplasty was used to assist recanalization were also excluded.
Patients underwent angiography and thrombolytic treatment with
the use of local anesthesia, aseptic technique, and digital
fluoroscopic control in a biplane angiographic suite. Sedatives
were avoided where possible. Methods of thrombolytic therapy
for patients included continuous infusion or pulse spray. Microcatheter
positioning relative to the thrombus was determined by the operator
but was typically within the thrombus. Mechanical methods for
clot disruption, such as balloon angioplasty or clot retrieval,
were not included. Thrombolytic agents infused in this study
were either intra-arterial tissue plasminogen activator (up
to 100 mg), urokinase (up to 1 million units), or pro-urokinase
(up to 1 million units).
Arteriograms performed before thrombolytic treatment were reviewed separately from arteriograms performed after thrombolytic treatment. Review of arteriograms before thrombolysis included identification of clot outline sign, site of occlusion, and extent of pial collaterals. Clot outline sign was defined as slow antegrade contrast opacification distal to the thrombus on the delayed images of the presenting arteriogram (Fig. 1). Presence of "clot outline sign" was made by evaluating the sequence of arteriographic images obtained during the pretreatment evaluation of the occlusion site. It implies that the vessel in question is almost completely occluded and has a minute blood flow past the clot. As is often the case, the vascular bed distal to the occlusion site is also perfused by pial collateral vessels. Site of occlusion was defined as either proximal or distal. Proximal occlusion included occlusions at the internal carotid artery, basilar artery, A1 segment, M1 segment, or P1 segment. All other occlusions were considered to be distal. Cerebral arterial segments are defined elsewhere.8 Post-thrombolysis arteriograms were reviewed to identify recanalization on the basis of a modified version of the TIMI flow grading scheme.9 No recanalization was given a grade of 0, minor recanalization (<33% of the territory recanalized) was a grade of 1, partial recanalization with reperfusion of more than 33% of the involved territory was a grade of 2, and complete recanalization with no visible vessel occlusion at the end of the procedure was a grade of 3. The presence of a clot outline sign was then correlated to modified TIMI (mTIMI) flow grade using contingency analysis, and Pearson correlation value was identified for significance. Logistic regression analysis for the mTIMI grade was performed that included presence of outline sign, age, site of occlusion, time to treatment, sex, presenting National Institutes of Health Stroke Scale (NIHSS) score, systolic blood pressure, platelet count on admission, presence of pial collaterals, and blood glucose value on admission. To facilitate regression analysis, NIHSS was treated as a continuous variable. The regression analyses were repeated using backward selection, and then variables with estimates having a probability of proving the null hypothesis greater than 0.2, based on the Wald test, were rejected.
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Fig 1. Prethrombolysis midarterial phase (A) and late arterial phase (B) angiographic images and post-thrombolysis angiographic image (C) from a patient who underwent intra-arterial thrombolysis with complete recanalization (C). This patient presented with a left m1 segment occlusion (A, arrow). Note the delayed opacification of the distal m1 and proximal m2 segments (arrows).
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Results
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A total of 87 of the 100 consecutive patients identified were
studied. Seven patients were excluded because arteriograms were
not available for review. In 3 patients, the microcatheter was
not able to reach the occlusion site. In 1 patient, the occluded
vessel was coiled as a result of intraprocedural perforation,
and 2 patients were excluded because angioplasty was used to
assist recanalization. Only 1 of the 6 patients in whom films
were available but were excluded had an outline sign present.
In that patient, the parent vessel was occluded with coils to
treat an iatrogenic perforation. The patients studied included
40 women and 47 men with a mean age of 65.1 (
= 14.4). The mean
time to treatment was 264.5 minutes (
= 84.0), median presenting
NIHSS was 16 (quartiles 11–20), mean platelet count on
admission value was 224 K/µL (
= 65.5), mean blood glucose
on admission value was 132 mg/dL (
= 49.8), and mean presenting
systolic blood pressure was 145.1 (
= 25.0). Occlusion sites
distributed as follows: middle cerebral artery (MCA), –71%;
internal carotid artery (ICA), 16%; anterior cerebral artery,
4% basilar artery, 1%; and posterior inferior cerebellar artery,
1%. Seventy-five percent of occlusions were proximal, and the
remaining 25% were distal. Nineteen of 87 patients with arteriograms
available for review displayed the clot outline sign. Thirteen
of these 19 (68.4%) went on to completely recanalize
(Table 1).
Only 20 (29.4%) of the 68 patients without demonstration of
the clot outline sign went on to complete recanalization. Eighteen
of 19 patients (94.7%) displaying the clot outline sign were
associated with a mTIMI grade of 2 or 3, whereas only 37 (54.4%)
of those without the clot outline sign were associated with
mTIMI grades of 2 or greater (
P = .0055). Logistic regression
analysis
Table 2 for mTIMI grades relative to other predictors
indicates that only the clot outline sign is significantly associated
with recanalization (
P = .0007).
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Table 1: Post-thrombolysis mTIMI grades in patients with angiographic demonstration of a clot outline sign versus those who did not demonstrate a clot outline sign
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Discussion
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Recanalization is a strong predictor for clinical outcome and
infarct volume after thrombolytic treatment.
1,3,5,10 Methods
used to recanalize patients have included intravenous and intra-arterial
thrombolysis, angioplasty, and clot retrieval. Recanalization
rates and clinical outcomes after intra-arterial thrombolysis
vary between studies depending on the type of thrombolytic agent,
technique, clot volume, and occlusion site.
11 Therefore, it
is important to identify predictors for improving recanalization
rates to determine treatment efficacy. Thus far, few investigations
have been able to identify predictors for recanalization. Although
MCA and ICA trunk occlusions have been shown to achieve successful
recanalization (mTIMI 2–3) more frequently than those
with distal occlusions by other investigators,
5–7 this
was not confirmed in this study. Initial angiographic morphologic
features have been shown to correlate with recanalization. In
a study performed by Pillai et al,
7 all 3 patients with "tram
track" appearance of the clot and 6 of 7 patients with "tapered"
appearance of clot had complete recanalization. Based on those
descriptions, it is evident that the "tram track" appearance
would qualify as the "outline sign" described in the current
work. It is also possible that some of the patients with "tapered"
appearance of the clot would also qualify as an "outline sign."
The current study evaluates contrast opacification distal to
the occlusion site rather than the angiographic morphology.
Unlike the descriptions of the "tram track" appearance and the
"tapered" appearance, the outline sign takes into account the
appearance of contrast distal to the occlusion site even on
delayed images rather than a single arteriographic picture.
It is significant that the observation in the current study
of "outline sign" was made after data were compiled, indicating
that this observation was made independently of other factors.
The number of patients included in the current study provides
statistically significant support for this finding. The cohort
of patients in this study included occlusions from all sites
of the brain, though most had MCA (71%) and ICA (16%) occlusions.
In this study, good recanalization (mTIMI 2–3) was evident
in 94.7% of patients with a clot outline sign, whereas only
54.4% of patients without the outline sign had mTIMI grades
of 2 and above
Table 1.
In the present study, predictors of recanalization tested included: presence of outline sign, age, site of occlusion, time to treatment (minutes), sex, presenting systolic blood pressure, presenting NIHSS score, admitting platelets, presence of pial collaterals, and admitting glucose value. Clinical studies have demonstrated that all of these variables are predictive of either clinical outcome or hemorrhage in acute stroke.1,3,12–24 As a result, they were included in our analysis. The only predictor that proved to have significance for recanalization among the variables tested in this study was clot outline sign Table 2. Support that contrast opacification distal to the occlusion site may be associated with higher recanalization rates is also found in coronary artery occlusions. TIMI grade 3 reperfusion is significantly higher in morphologic descriptions in which there is contrast-opacifying vasculature distal to the occlusion site.25
Because only endovascular pharmacologic treatment was used for thrombolysis in this study, it is not known whether the presence of an "outline sign" would be associated with higher recanalization rates with mechanical thrombolysis. If a difference did exist, presence of "outline sign" may influence the selection of treatment method and help the operator make a decision on endovascular treatment method. Although the prognostic value for the "clot outline sign" was not investigated in this study, it is suspected that its association with higher recanalization rates would account for any potential clinical changes. It is assumed that the miniscule blood flow around the blood clot in patients with this sign would not account for any independent differences in clinical outcome.
In the current study, there are several limitations. The dataset was compiled retrospectively and therefore is prone to misclassification bias. To reduce this bias, prethrombolysis arteriograms were reviewed separately from postthrombolysis arteriograms, thereby blinding the reviewer from outcome. A total of 13 patients were excluded; however, these patients had baseline characteristics similar to those of the study population, and therefore no bias was introduced in the study selection. The study population is heterogeneous in that the patients received 1 of 3 intra-arterial thrombolytic agents; however, most were given tissue plasminogen activator. In addition, patients had occlusions in both proximal and distal sites. These differences were taken into account when performing analysis, and therefore allowed the comparison of the clot outline sign with recanalization rates. Other factors that may affect recanalization have not been studied, such as source or makeup of clot and operator performing the procedure. Because of the overwhelming difference in recanalization rates when the clot outline sign was present, it is not likely that such factors would substantially affect our conclusions.
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Conclusion
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Prethrombolysis arteriography demonstrating delayed antegrade
contrast opacification distal to the occlusion site is associated
with higher recanalization rates after local intra-arterial
administration of thrombolytic agents. This angiographic finding
can provide an objective means to assess potential for recanalization
before thrombolytic treatment.
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Acknowledgments
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We thank Peggy Notestine, Hoda Jradi, Donald Chakeres, Eric
Bourekas, and Wayne Slone.
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Footnotes
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This work has been presented previously at the 2005 meeting
of the American Society of Interventional and Therapeutic Neuroradiology;
May 20–22, 2005; Toronto, Canada, and at the 42nd Annual
Meeting of the American Society of Neuroradiology; June 5–11,
2004.
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Received August 19, 2005;
accepted after revision November 13, 2005.
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Abstract
Introduction