Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome

Background and Purpose— The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods— This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin Scale score of ⩽2). Additional outcomes include the full range of the modified Rankin Scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results— Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26–1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant (P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions— In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

[1]  M. Cipolla,et al.  ACE (Angiotensin-Converting Enzyme) Inhibition Reverses Vasoconstriction and Impaired Dilation of Pial Collaterals in Chronic Hypertension , 2020, Hypertension.

[2]  Albert van der Zwan,et al.  Anatomy and Functionality of Leptomeningeal Anastomoses: A Review , 2003, Stroke.

[3]  M E Moseley,et al.  Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic resonance imaging. , 2001, Archives of neurology.

[4]  G. Zaharchuk,et al.  Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort , 2014, Stroke.

[5]  G. Albers,et al.  Response by de Havenon et al to Letter Regarding Article, "Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome". , 2019, Stroke.

[6]  S M Davis,et al.  Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted MRI , 1998, Neurology.

[7]  D. Liebeskind,et al.  Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[8]  Max Wintermark,et al.  Demographic and clinical predictors of leptomeningeal collaterals in stroke patients. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[9]  J. Faber,et al.  Wide Genetic Variation in the Native Pial Collateral Circulation is a Major Determinant of Variation in Severity of Stroke , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  Gelin Xu,et al.  Predictors for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Acute Ischemic Stroke , 2017, Stroke.

[11]  D. Liebeskind,et al.  Impact of Time-to-Reperfusion on Outcome in Patients with Poor Collaterals , 2015, American Journal of Neuroradiology.

[12]  G. Zaharchuk,et al.  Effect of Collateral Blood Flow on Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke , 2014, Stroke.

[13]  D. Liebeskind,et al.  Systematic Review of Methods for Assessing Leptomeningeal Collateral Flow , 2012, American Journal of Neuroradiology.

[14]  M. Cipolla,et al.  Pial Collateral Reactivity During Hypertension and Aging , 2016, Stroke.

[15]  D. Liebeskind Collaterals in acute stroke: beyond the clot. , 2005, Neuroimaging clinics of North America.

[16]  B. Menon,et al.  Displaying Multiphase CT Angiography Using a Time-Variant Color Map: Practical Considerations and Potential Applications in Patients with Acute Stroke , 2020, American Journal of Neuroradiology.

[17]  F. Ricolfi,et al.  Collateral circulation in acute stroke: assessing methods and impact: a literature review. , 2014, Journal of neuroradiology. Journal de neuroradiologie.

[18]  N. Venketasubramanian,et al.  Assessment of Intracranial Collaterals on CT Angiography in Anterior Circulation Acute Ischemic Stroke , 2015, American Journal of Neuroradiology.

[19]  Gregory W Albers,et al.  Late Window Paradox. , 2018, Stroke.

[20]  Min Lou,et al.  The Prognostic Value of a Four-Dimensional CT Angiography-Based Collateral Grading Scale for Reperfusion Therapy in Acute Ischemic Stroke Patients , 2016, PloS one.

[21]  Gyeong-Moon Kim,et al.  Selection of Candidates for Endovascular Treatment: Characteristics According to Three Different Selection Methods , 2019, Journal of stroke.

[22]  F Viñuela,et al.  Impact of collateral flow on tissue fate in acute ischaemic stroke , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[23]  A. Demchuk,et al.  CT Angiography Clot Burden Score and Collateral Score: Correlation with Clinical and Radiologic Outcomes in Acute Middle Cerebral Artery Infarct , 2009, American Journal of Neuroradiology.

[24]  K. Furie,et al.  Collateral Vessels on CT Angiography Predict Outcome in Acute Ischemic Stroke , 2009, Stroke.

[25]  Scott Hamilton,et al.  A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3) , 2017, International journal of stroke : official journal of the International Stroke Society.

[26]  A. Demchuk,et al.  Multiphase CT Angiography: A New Tool for the Imaging Triage of Patients with Acute Ischemic Stroke. , 2015, Radiology.

[27]  T. Jovin,et al.  Fast Versus Slow Progressors of Infarct Growth in Large Vessel Occlusion Stroke: Clinical and Research Implications , 2017, Stroke.

[28]  Eric E. Smith,et al.  Leptomeningeal collaterals are associated with modifiable metabolic risk factors , 2013, Annals of neurology.

[29]  A. Demchuk,et al.  Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging , 2018, The New England journal of medicine.

[30]  A. Demchuk,et al.  Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial , 2015, Stroke.

[31]  M. Cipolla,et al.  Effect of hypertension and peroxynitrite decomposition with FeTMPyP on CBF and stroke outcome , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  David L. Aylor,et al.  Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains , 2019, Genetics.