Relationship between the degree of recanalization and functional outcome in acute ischemic stroke is mediated by penumbra salvage volume

Abstract Background The presence of metabolically viable brain tissue that may be salvageable with rapid cerebral blood flow restoration is the fundament rationale for reperfusion therapy in patients with large vessel occlusion stroke. The effect of endovascular treatment (EVT) on functional outcome largely depends on the degree of recanalization. However, the relationship of recanalization degree and penumbra salvage has not yet been investigated. We hypothesized that penumbra salvage volume mediates the effect of thrombectomy on functional outcome. Methods 99 acute anterior circulation stroke patients who received multimodal CT and underwent thrombectomy with resulting partial to complete reperfusion (modified thrombolysis in cerebral infarction scale (mTICI) ≥ 2a) were retrospectively analyzed. Penumbra volume was quantified on CT perfusion and penumbra salvage volume (PSV) was calculated as difference of penumbra and net infarct growth from admission to follow-up imaging. Results In patients with complete reperfusion (mTICI ≥ 2c), the median PSV was significantly higher than the median PSV in patients with partial or incomplete (mTICI 2a–2b) reperfusion (median 224 mL, IQR: 168–303 versus 158 mL, IQR: 129–225; p < 0.01). A higher degree of recanalization was associated with increased PSV (+ 63 mL per grade, 95% CI: 17–110; p < 0.01). Higher PSV was also associated with improved functional outcome (OR/mRS shift: 0.89; 95% CI: 0.85–0.95, p < 0.0001). Conclusions PSV may be an important mediator between functional outcome and recanalization degree in EVT patients and could serve as a more accurate instrument to compare treatment effects than infarct volumes.

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Association of collateral status and ischemic core growth in patients with acute ischemic stroke

Neurology ◽

10.1212/wnl.0000000000011258 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011258

Author(s):

Longting Lin ◽

Jianhong Yang ◽

Chushuang Chen ◽

Huiqiao Tian ◽

Andrew Bivard ◽

...

Keyword(s):

Growth Rate ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Ct Perfusion ◽

Study Cohort ◽

Vessel Occlusion ◽

Ischemic Core ◽

Relationship Of ◽

The Relationship ◽

Linear Regressions

ObjectiveTo test the hypothesis that acute ischemic patients with poorer collaterals would have faster ischemic core growth, we included 2 cohorts in the study, cohort 1 of 342 patients for derivation and cohort 2 of 414 patients for validation purpose.MethodsAcute ischemic stroke patients with large vessel occlusion were included. Core growth rate was calculated by the following equation: Core growth rate = Acute core volume on CTP/Time from stroke onset to CTP. Collateral status was assessed by the ratio of severe hypoperfusion volume within the hypoperfusion region of CTP. The CTP collateral index was categorized in tertiles; for each tertile, core growth rate was summarized as median and inter-quartile range. Simple linear regressions were then performed to measure the predictive power of CTP collateral index in core growth rate.ResultsFor patients allocated to good collateral on CT perfusion (tertile 1 of collateral index), moderate collateral (tertile 2), and poor collateral (tertile 3), the median core growth rate was 2.93 mL/h (1.10–7.94), 8.65 mL/h (4.53–18.13), and 25.41 mL/h (12.83–45.07) respectively. Increments in the collateral index by 1% resulted in an increase of core growth by 0.57 mL/h (coefficient = 0.57, 95% confidence interval = [0.46, 0.68], p < 0.001). The relationship of core growth and CTP collateral index was validated in cohort 2. An increment in collateral index by 1% resulted in an increase of core growth by 0.59 mL/h (coefficient = 0.59 [0.48–0.71], p < 0.001) in cohort 2.ConclusionCollateral status is a major determinant of ischemic core growth.

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Topographic correlation of infarct area on CT perfusion with functional outcome in acute ischemic stroke

Journal of Neurosurgery ◽

10.3171/2018.8.jns181095 ◽

2020 ◽

Vol 132 (1) ◽

pp. 33-41 ◽

Cited By ~ 3

Author(s):

Neil Haranhalli ◽

Nnenna Mbabuike ◽

Sanjeet S. Grewal ◽

Tasneem F. Hasan ◽

Michael G. Heckman ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Ct Perfusion ◽

Multivariable Analysis ◽

Reperfusion Therapy ◽

Infarct Core ◽

Anterior Circulation ◽

Logistic Regression Models ◽

Confounding Variables

OBJECTIVEThe role of CT perfusion (CTP) in the management of patients with acute ischemic stroke (AIS) remains a matter of debate. The primary aim of this study was to evaluate the correlation between the areas of infarction and penumbra on CTP scans and functional outcome in patients with AIS.METHODSThis was a retrospective review of 100 consecutively treated patients with acute anterior circulation ischemic stroke who underwent CT angiography (CTA) and CTP at admission between February 2011 and October 2014. On CTP, the volume of ischemic core and penumbra was measured using the Alberta Stroke Program Early CT Score (ASPECTS). CTA findings were also noted, including the site of occlusion and regional leptomeningeal collateral (rLMC) score. Functional outcome was defined by modified Rankin Scale (mRS) score obtained at discharge. Associations of CTP and CTA parameters with mRS scores at discharge were assessed using multivariable proportional odds logistic regression models.RESULTSThe median age was 67 years (range 19–95 years), and the median NIH Stroke Scale score was 16 (range 2–35). In a multivariable analysis adjusting for potential confounding variables, having an infarct on CTP scans in the following regions was associated with a worse mRS score at discharge: insula ribbon (p = 0.043), perisylvian fissure (p < 0.001), motor strip (p = 0.007), M2 (p < 0.001), and M5 (p = 0.023). A worse mRS score at discharge was more common in patients with a greater volume of infarct core (p = 0.024) and less common in patients with a greater rLMC score (p = 0.004).CONCLUSIONSThe results of this study provide evidence that several CTP parameters are independent predictors of functional outcome in patients with AIS and have potential to identify those patients most likely to benefit from reperfusion therapy in the treatment of AIS.

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Abstract TP91: Unfavorable Baseline Hypoperfusion Intensity Ratio is Associated With Infarct Growth and Poor Outcome in Patients With Distal MCA Occlusions

Stroke ◽

10.1161/str.51.suppl_1.tp91 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Adam MacLellan ◽

Michael Mlynash ◽

Stephanie Kemp ◽

Soren Christensen ◽

Michael Marks ◽

...

Keyword(s):

Functional Outcome ◽

Intensity Ratio ◽

Ct Perfusion ◽

Anterior Circulation ◽

Excellent Functional Outcome ◽

The Mean ◽

Ischemic Core ◽

Core Volume ◽

Distal Middle Cerebral Artery

Background: A low hypoperfusion intensity ratio (HIR) predicts good collateral vessel status and correlates with infarct growth and functional outcome in early window patients with proximal large vessel anterior circulation occlusions. Its performance in predicting clinical and radiologic outcome has not been assessed in patients with more distal occlusions. In this retrospective analysis of the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke (CRISP) study, we hypothesized that a favorable baseline HIR would predict less infarct growth in patients with distal middle cerebral artery (MCA) occlusions. Methodology: Patients with occlusions of an M2 or M3 branch of the MCA on catheter angiography were included; all patients underwent mechanical thrombectomy with TICI2B/3 reperfusion. Baseline ischemic core volume and HIR (Tmax >10s / Tmax >6s) were assessed with RAPID software; late follow-up infarct volumes (>36 hours from initial CT perfusion) were manually determined from DWI MRI. Excellent functional outcome was defined as a modified Rankin score of 0-1. Results: Fourteen patients with baseline perfusion and late follow-up imaging were included; nine patients presented with M2 occlusions, and 5 with M3 occlusions. The mean baseline HIR of 0.48 was used to dichotomize patients into favorable or unfavorable baseline profiles. Patients with a favorable baseline HIR had significantly smaller baseline ischemic core volumes (0 mL [IQR 0-3.3] vs. 14.0 mL [IQR 8.7-22.1], p=0.01), smaller final infarct volumes (16.1 mL [IQR 12.7-41.2] vs. 71.4 mL [IQR 43.8-113.5], p=0.01) and less infarct growth (16.1 mL [IQR 9.4-31.9] vs. 49.0 mL [IQR 31.1-100.8], p=0.03). Excellent functional outcome was achieved in 6/6 (100%) of those with favorable baseline HIR, versus 3/8 (37.5%) with unfavorable baseline profile (p=0.03). Conclusion: In patients with distal MCA occlusions, poor collateral status at baseline as demonstrated by a high HIR score is associated with more infarct growth and worse clinical outcomes. HIR may be helpful for guiding thrombectomy decisions in patients with distal occlusions and warrants further prospective study in this population.

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Neutrophil-Lymphocyte Ratio Predicts Functional and Safety Outcomes after Endovascular Treatment for Acute Ischemic Stroke

Cerebrovascular Diseases ◽

10.1159/000489401 ◽

2018 ◽

Vol 45 (5-6) ◽

pp. 221-227 ◽

Cited By ~ 22

Author(s):

Zhenhui Duan ◽

Huaiming Wang ◽

Zhen Wang ◽

Yonggang Hao ◽

Wenjie Zi ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Functional Outcome ◽

Laboratory Data ◽

Poor Functional Outcome ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

The Relationship

Background and Objective: Endovascular treatment (EVT) is proven to be safe and effective for treating acute large vessel occlusion stroke (LVOS). The neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, which plays an important role in the process of treating ischemic stroke. This study aims to explore the relationship between NLR and the clinical outcomes of LVOS patients undergoing EVT. Methods: Patients were selected from the EVT for acUte Anterior circuLation (ACTUAL) ischemic stroke registry. The laboratory data (neutrophil count, lymphocyte count) before EVT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3–6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR with functional outcome, symptomatic intracranial hemorrhage (sICH), and mortality. Results: We eventually included 616 patients (median of age, 66 years; 40.3% female). There were 350 (56.7%) patients achieving mRS of 3–6 at 3 months, 98 (15.9%) patients with sICH, and the mortality at 3 months was 24.8% (153/616). Baseline NLR was independently associated with poor functional outcome (OR 1.58; 95% CI 1.02–2.45; p = 0.039) and sICH (OR 1.84; 95% CI 1.09–3.11; p = 0.023) but showed a trend for predicting 3-month mortality (OR 1.57; 95% CI 0.94–2.65; p = 0.088). Conclusions: NLR independently predicts 3-month functional outcome and sICH but the existence of a trend association with mortality after EVT for acute anterior circulation LVOS patients.

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CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2016-012628 ◽

2016 ◽

Vol 9 (10) ◽

pp. 940-943 ◽

Cited By ~ 19

Author(s):

Fabrizio Sallustio ◽

Caterina Motta ◽

Silvia Pizzuto ◽

Marina Diomedi ◽

Angela Giordano ◽

...

Keyword(s):

Ct Angiography ◽

Mechanical Thrombectomy ◽

Collateral Flow ◽

Large Artery ◽

Anterior Circulation ◽

Conventional Angiography ◽

Multivariable Analyses ◽

Relationship Of ◽

The Relationship

BackgroundCollateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy.MethodsBaseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals.ResultsEvaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0–2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome.ConclusionsCTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.

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Abstract WP68: CT Perfusion Collateral Index in Assessment of Collaterals in Patients With Acute Ischemic Stroke: A New Imaging Biomarker

Stroke ◽

10.1161/str.51.suppl_1.wp68 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Kambiz Nael ◽

Jonathan Larson ◽

Yu Sakai ◽

Jared Goldstein ◽

Jacob Deutsch ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Ct Perfusion ◽

Imaging Biomarker ◽

Collateral Flow ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Good Functional Outcome ◽

Infarction Volume

Purpose: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral flow. We aim to evaluate the collateral status via CT-based PCI in association with outcome measures such as final infraction volume, recanalization status and functional outcome in patients presenting with acute ischemic stroke (AIS) and in a comparative analysis against CTA and DSA collateral scores. Methods: AIS patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. CTA collateral scores were calculated using modified Tan score and DSA collateral scores were evaluated by ASITN grading. In addition, previously described PCI defined as the volume of moderately hypoperfused tissue (ATD 2-6sec ) multiplied by its corresponding rCBV was calculated in each patient. The association of CTA and DSA collateral scores and PCI were assessed against 3 measured outcomes: 1) Final infarction volume obtained from follow up MRI; 2) Final recanalization status defined by TICI scores; 3) Functional outcome measured by 90-day mRS. Results: A total of 53 patients met inclusion criteria (27F; mean/SD age: 70.1 ± 13 years; median NIHSS: 14). Final infarction volume (mean/SD: 30/40 mL), excellent recanalization defined by TICI >2C was achieved in 36 (68%) patients, and 23 patients (43%) had good functional outcome (mRS <2). Having good collaterals on all 3 modalities (CTA, DSA, CTP-PCI) were associated with significantly (p<0.05) smaller infarction volume. However only good collaterals determined by CTP-PCI was predictive of achieving excellent recanalization (p=0.001) or good functional outcome (p=0.01) ( Figure 1 ). Conclusion: Collateral status assessed via CT-PCI outperforms CTA and DSA collateral scores in prediction of excellent recanalization and good functional outcome and may be a promising imaging biomarker of collateral status in patients with AIS.

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Relationship of Volume of Lesion to Length of Hospital Stay and Outcome at One Year in Stroke Patients

Scottish Medical Journal ◽

10.1177/003693300104600609 ◽

2001 ◽

Vol 46 (6) ◽

pp. 178-183 ◽

Cited By ~ 1

Author(s):

J.M. Maddox ◽

R.S. MacWalter ◽

A.D. McMahon

Keyword(s):

Hospital Stay ◽

Functional Outcome ◽

Univariate Analysis ◽

Length Of Hospital Stay ◽

Lesion Volume ◽

Functional Outcome Measures ◽

One Year ◽

Relationship Of ◽

The Relationship

The aim of this study was to investigate the relationship between the volume of lesion (VOL) in patients with stroke and the associated length of hospital stay (LOS), as well as longer-term functional outcome. Computerised tomography (CT) scans were used to measure the volume, region and type of lesion, volume being measured by planimetry. LOS and other patient details were obtained from the Dundee Stroke Database. The total LOS was associated with the VOL on univariate analysis (p=0.004) and after adjustment for the other variables (p-0.006) due to a larger lesion being associated with longer stay in hospital. Patient follow-up confirmed that the VOL was also highly significant when related to functional outcome measures of impairment, disability and handicap at one year, as determined by Orgogozo (p=0.03), Barthel (p<0.01) and Rankin scores (p<0.01) respectively. The VOL is related to the length of stay in hospital and outcome at one year. This is of particular interest with the increasing use of thrombolysis and development of neuroprotectant agents designed to limit VOL.

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Abstract TP40: Time From Stroke Onset to Reperfusion is Associated With Worse Functional Outcomes in Patients With Rapidly Progressing Infarcts

Stroke ◽

10.1161/str.51.suppl_1.tp40 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Anson Wang ◽

Sumita Strander ◽

Sreeja Kodali ◽

Andrew Silverman ◽

Alexandra Kimmel ◽

...

Keyword(s):

Functional Outcome ◽

Symptom Onset ◽

Functional Outcomes ◽

Time Window ◽

Ct Perfusion ◽

Infarct Volume ◽

Acute Stroke Care ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Slow Progressors

Introduction: Recent trials have demonstrated the benefit of endovascular therapy (EVT) beyond 6 hours of symptom onset. However, the importance of time to reperfusion (TTR) in the extended time window has recently been questioned. Given the variability of infarct growth rate (IGR), the time delay until reperfusion may have greater consequences for those with rapidly progressing infarcts, and identifying such patients is essential for improving outcomes. We tested the hypothesis that TTR is more closely associated with functional outcome in patients with rapidly progressing infarcts compared to their slow-progressing counterparts. Methods: We retrospectively identified 106 patients at our center’s prospectively collected stroke database with anterior circulation large-vessel occlusion stroke and known time of symptom onset. Patients underwent initial CT perfusion imaging (CTP), EVT and and follow-up MRI at 24 hours. Core infarct volumes at presentation (CBF<30%) were estimated using RAPID software. The time between symptom onset and CTP was used to estimate IGR and to categorize patients as fast (≥5 mL/hour) or slow (<5 mL/hour) progressors. Alternatively, final infarct volume (FIV) was measured on MRI and used to calculate IGR in the absence of CTP. Functional outcome was assessed using the modified Rankin scale (mRS) at discharge and 90 days. Associations were computed using ordinal regression adjusting for age, ASPECTS, and TICI. Results: 35 fast progressors (age 71±14, 17 F, TTR 288±91 minutes, mean IGR 21±24 mL/hour) and 71 slow progressors (age 71±17, 48 F, TTR 374±211 minutes, mean IGR 1.0±1.5 mL/hour) were identified. Fast progressors had higher admission NIHSS scores (18±6 vs 13±7, p<0.001) and significantly larger FIV (101±77 vs 47±65 mL, p<0.001). After adjusting for baseline factors, TTR was significantly associated with worse functional outcome at 90 days in fast progressors (p=0.026, aOR 1.13 per 10 minutes, 95% CI 1.02-1.28), but not for slow progressors (p=0.708). Conclusions: In patients with rapidly progressing infarcts (≥5 mL/hour), TTR was associated with worse functional outcomes at 90 days compared to slow progressors. Identifying such patients may be critical for appropriate triage and rapid delivery of acute stroke care.

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A Decade of Disparities in Diabetes Technology Use and HbA1c in Pediatric Type 1 Diabetes: A Trans-Atlantic Comparison

10.2337/figshare.12808301 ◽

2020 ◽

Author(s):

Ananta Addala ◽

Marie Auzanneau ◽

Kellee Miller ◽

Werner Maier ◽

Nicole Foster ◽

...

Keyword(s):

Type 1 Diabetes ◽

Technology Use ◽

Hemoglobin A1c ◽

Diabetes Technology ◽

Design And Methods ◽

Relationship Of ◽

The Relationship ◽

Pediatric Type 1 Diabetes

Objective: As diabetes technology use in youth increases worldwide, inequalities in access may exacerbate disparities in hemoglobin A1c (HbA1c). We hypothesized an increasing gap in diabetes technology use by socioeconomic status (SES) would be associated with increased HbA1c disparities. Research Design and Methods: Participants aged <18 years with diabetes duration ≥1 year in the Type 1 Diabetes Exchange (T1DX, US, n=16,457) and Diabetes Prospective Follow-up (DPV, Germany, n=39,836) registries were categorized into lowest (Q1) to highest (Q5) SES quintiles. Multiple regression analyses compared the relationship of SES quintiles with diabetes technology use and HbA1c from 2010-2012 and 2016-2018. Results: HbA1c was higher in participants with lower SES (in 2010-2012 & 2016-2018, respectively: 8.0% & 7.8% in Q1 and 7.6% & 7.5% in Q5 for DPV; and 9.0% & 9.3% in Q1 and 7.8% & 8.0% in Q5 for T1DX). For DPV, the association between SES and HbA1c did not change between the two time periods, whereas for T1DX, disparities in HbA1c by SES increased significantly (p<0.001). After adjusting for technology use, results for DPV did not change whereas the increase in T1DX was no longer significant. Conclusions: Although causal conclusions cannot be drawn, diabetes technology use is lowest and HbA1c is highest in those of the lowest SES quintile in the T1DX and this difference for HbA1c broadened in the last decade. Associations of SES with technology use and HbA1c were weaker in the DPV registry.

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Normative distribution of posterior circulation tissue time-to-maximum: Effects of anatomic variation, tracer kinetics, and implications for patient selection in posterior circulation ischemic stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20982395 ◽

2021 ◽

pp. 0271678X2098239

Author(s):

Adam E Goldman-Yassen ◽

Matus Straka ◽

Michael Uhouse ◽

Seena Dehkharghani

Keyword(s):

Ischemic Stroke ◽

Selection Criteria ◽

Arterial Input Function ◽

Anatomic Variation ◽

Input Function ◽

Posterior Circulation ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Perfusion Time

The generalization of perfusion-based, anterior circulation large vessel occlusion selection criteria to posterior circulation stroke is not straightforward due to physiologic delay, which we posit produces physiologic prolongation of the posterior circulation perfusion time-to-maximum (Tmax). To assess normative Tmax distributions, patients undergoing CTA/CTP for suspected ischemic stroke between 1/2018-3/2019 were retrospectively identified. Subjects with any cerebrovascular stenoses, or with follow-up MRI or final clinical diagnosis of stroke were excluded. Posterior circulation anatomic variations were identified. CTP were processed in RAPID and segmented in a custom pipeline permitting manually-enforced arterial input function (AIF) and perfusion estimations constrained to pre-specified vascular territories. Seventy-one subjects (mean 64 ± 19 years) met inclusion. Median Tmax was significantly greater in the cerebellar hemispheres (right: 3.0 s, left: 2.9 s) and PCA territories (right: 2.9 s; left: 3.3 s) than in the anterior circulation (right: 2.4 s; left: 2.3 s, p < 0.001). Fetal PCA disposition eliminated ipsilateral PCA Tmax delays (p = 0.012). Median territorial Tmax was significantly lower with basilar versus any anterior circulation AIF for all vascular territories (p < 0.001). Significant baseline delays in posterior circulation Tmax are observed even without steno-occlusive disease and vary with anatomic variation and AIF selection. The potential for overestimation of at-risk volumes in the posterior circulation merits caution in future trials.

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