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June 07, 2022; 98 (23) Research Article

The Cerebral Collateral Cascade

Comprehensive Blood Flow in Ischemic Stroke

Tobias Djamsched Faizy, Michael Mlynash, Reza Kabiri, Soren Christensen, Gabriella Marie Kuraitis, View ORCID ProfileMarius M. Mader, Fabian Flottmann, Gabriel Broocks, View ORCID ProfileMaarten G. Lansberg, Gregory W. Albers, Michael P. Marks, View ORCID ProfileJens Fiehler, Max Wintermark, View ORCID ProfileJeremy J. Heit
First published April 28, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200340
Tobias Djamsched Faizy
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD, PhD
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Michael Mlynash
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD, BSc
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Reza Kabiri
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
BSc
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Soren Christensen
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
PhD
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Gabriella Marie Kuraitis
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
BSc
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Marius M. Mader
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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  • ORCID record for Marius M. Mader
Fabian Flottmann
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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Gabriel Broocks
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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Maarten G. Lansberg
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
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Gregory W. Albers
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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Michael P. Marks
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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Jens Fiehler
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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Max Wintermark
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD
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Jeremy J. Heit
From the Departments of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.) and Neurology and Neurological Sciences (M.M., S.C., M.G.L., G.W.A.), Stanford University School of Medicine, CA; and Departments of Neuroradiology (T.D.F., R.K., F.F., G.B., J.F.) and Neurosurgery (M.M.M.), University Medical Center Hamburg-Eppendorf, Germany.
MD, PhD
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  • ORCID record for Jeremy J. Heit
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Citation
The Cerebral Collateral Cascade
Comprehensive Blood Flow in Ischemic Stroke
Tobias Djamsched Faizy, Michael Mlynash, Reza Kabiri, Soren Christensen, Gabriella Marie Kuraitis, Marius M. Mader, Fabian Flottmann, Gabriel Broocks, Maarten G. Lansberg, Gregory W. Albers, Michael P. Marks, Jens Fiehler, Max Wintermark, Jeremy J. Heit
Neurology Jun 2022, 98 (23) e2296-e2306; DOI: 10.1212/WNL.0000000000200340

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Abstract

Background and Objectives Robust cerebral collaterals are associated with favorable outcomes in patients with acute ischemic stroke due to large vessel occlusion treated by thrombectomy. However, collateral status assessment mostly relies on single imaging biomarkers and a more comprehensive holistic approach may provide deeper insights into the biology of collateral perfusion on medical imaging. Comprehensive collateralization is defined as blood flow of cerebral arteries through the brain tissue and into draining veins. We hypothesized that a comprehensive analysis of the cerebral collateral cascade (CCC) on an arterial, tissue, and venous level would predict clinical and radiologic outcomes.

Methods This was a multicenter retrospective cohort study of patients with acute stroke undergoing thrombectomy triage. CCC was determined by quantifying pial arterial collaterals, tissue-level collaterals, and venous outflow (VO). Pial arterial collaterals were determined by CT angiography; tissue-level collaterals were assessed on CT perfusion. VO was assessed on CT angiography using the cortical vein opacification score. Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and VO), CCC− (poor pial collaterals, tissue-level collaterals, and VO), and CCCmixed (the remainder of the patients). Primary outcome was functional independence (modified Rankin Scale score 0–2) at 90 days. Secondary outcome was final infarct volume.

Results A total of 647 patients met inclusion criteria: 176 CCC+, 345 CCCmixed, and 126 CCC−. Multivariable ordinal logistic regression showed that CCC+ predicted good functional outcomes (odds ratio [OR] 18.9 [95% CI 8–44.5]; p < 0.001) compared with CCC− and CCCmixed. CCCmixed patients likely had better functional outcomes compared with CCC− patients (OR 2.5 [95% CI 1.2–5.4]; p = 0.014). Quantile regression analysis (50th percentile) showed that CCC+ (β −78.5, 95% CI −96.0 to −61.1; p < 0.001) and CCCmixed (β −64.0, 95% CI −82.4 to −45.6; p < 0.001) profiles were associated with considerably lower final infarct volumes compared with CCC− profiles.

Discussion Comprehensive assessment of the collateral blood flow cascade in patients with acute stroke is a strong predictor of clinical and radiologic outcomes in patients treated by thrombectomy.

Glossary

ASPECTS=
Alberta Stroke Program Early CT Score;
CCC=
cerebral collateral cascade;
AIS=
acute ischemic stroke;
HIR=
hypoperfusion intensity ratio;
ICA=
internal carotid artery;
IQR=
interquartile range;
LVO=
large vessel occlusion;
M1=
first segment of the middle cerebral artery;
M2=
second segment of the middle cerebral artery;
mRS=
modified Rankin Scale;
mTICI=
modified Thrombolysis in Cerebral Infarction;
NIHSS=
National Institutes of Health Stroke Scale;
OR=
odds ratio;
Tmax=
time to maximum;
VO=
venous outflow

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Brad Worrall, MD, MSc, FAAN.

  • Editorial, page 955

  • Received September 16, 2021.
  • Accepted in final form February 21, 2022.
  • © 2022 American Academy of Neurology
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