Abstract 131: TICI 2A Reperfusion Increases Risk of Parenchymal Hemorrhage After Endovascular Treatment for Acute Ischemic Stroke

Background: Endovascular reperfusion therapy (ERT) for acute large vessel occlusion limits infarct expansion and improves clinical outcomes but successful reperfusion may also increase risk of reperfusion injury and parenchymal hemorrhage (PH). We explored the association between levels of reperfusion and risk of PH. Methods: In a post-hoc analysis of the endovascular arm of the Interventional Management of Stroke-III randomized clinical trial, we assessed the association between levels of reperfusion (TICI0-1, 2A and 2B/3) and hemorrhage risk (PH1/2) in unadjusted and adjusted models controlling for stroke severity, final infarct volume (FIV) and level of occlusion. Results: Out of 434 participants who received ERT, 311 had documented TICI reperfusion grades (TICI 0-1: 84 [27%], TICI 2A: 108 [34.7%], TICI 2B/3: 119 [38.3%]). PH occurred in 42 (13.5%) patients. Patient characteristics are shown in Figure A. Higher reperfusion scores were associated with lower FIV (N=264, Mann-Whitney p<0.001 Figure B). Univariable predictors (p<0.10) of PH included FIV (p<0.0001), 24-hour NIHSS (p<0.0001) and TICI reperfusion grade (p=0.08). Compared to the TICI 0-1 group, TICI 2A was associated with higher odds of PH (OR=3.9, 1.26-12.1, p=0.014) while odds of PH in TICI 2B/3 reperfusion was similar to the TICI 0-1 category (OR=1.76, 0.73-4.26, p=0.2) after controlling for FIV or 24-hour NIHSS (Fig. C). Conclusions: Risk of PH appears to be highest in patients with intermediate levels of reperfusion even after adjusting for infarct size. While the reasons for this need investigating, we propose that the infarct size-mitigating effect of intermediate reperfusion may be partially offset by increased risk of PH. Our exploratory results emphasize the importance of achieving complete reperfusion during the treatment of acute LVO stroke patients.

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Abstract WP142: Intravenous Tissue Plasminogen Activator for Patients with Mild and Rapidly Improving Ischemic Strokes and Large Vessel Occlusions: Examining In-hospital Outcomes

Stroke ◽

10.1161/str.48.suppl_1.wp142 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Jeffrey Wagner ◽

Constance McGraw ◽

Kathryn McCarthy ◽

Judd Jensen ◽

Alessandro Orlando ◽

...

Keyword(s):

Hospital Mortality ◽

Heart Association ◽

Patient Characteristics ◽

Large Vessel ◽

Stroke Severity ◽

Vessel Occlusion ◽

Intravenous Tissue Plasminogen Activator ◽

Increased Risk ◽

Comprehensive Stroke Center ◽

Stroke Center

Background: Upon hospital arrival, patients with mild or rapidly improving acute ischemic strokes (AIS) are frequently not treated with IV-tPA. Recent guidelines from the American Heart Association report that diagnosis on imaging of large vessel occlusion (LVO) despite mild stroke severity leads to increased risk of poorer outcomes. The objective of our study was to examine outcomes following tPA in this AIS population. Methods: The study included all AIS patients with an admission NIHSS ≤7 and diagnosis of a LVO on imaging from a single comprehensive stroke center between 2010-2016. Patients were excluded due to missing contraindications to tPA or with a symptom to arrival time of >4.5 hours (n=234). We compared patients who received tPA to those who received no treatment because of mild or rapidly improving symptoms. Outcomes were sICH, improvement in NIHSS score, discharge mRS ≤2, and in-hospital mortality. Patient characteristics were compared univariately, and step-wise logistic regression was used to adjust for confounding variables. Entry criterion was P=0.2 and exit criterion was P=0.07. Results: There were 76 patients with an AIS diagnosis of LVO. Of these patients, 39 (51%) were treated with tPA and 37 (49%) were not treated. Overall, the median (IQR) age was 72 (61-82.5). Patients treated with tPA had a median admission NIHSS of 5 (3-6), and a larger proportion were male (77%) and smokers (4%). Patients without tPA treatment had a median NIHSS of 2 (1-3), and a larger proportion had hypertension (49%). All outcomes were not significantly different between groups after adjustment (Table 1). There were no patients with sICH. Conclusions: Our study suggests that tPA in mild LVO patients does not introduce additional risk in terms of sICH, in-hospital mortality, change in NIHSS, or discharge mRS. Further justification for withholding tPA in this group should be based on 90-day mRS scores, in order to better understand long-term functional outcomes.

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Progression of cerebral infarction before and after thrombectomy is modified by prehospital pathways

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-017155 ◽

2021 ◽

pp. neurintsurg-2020-017155

Author(s):

Alexander M Kollikowski ◽

Franziska Cattus ◽

Julia Haag ◽

Jörn Feick ◽

Alexander G März ◽

...

Keyword(s):

Patient Characteristics ◽

Large Vessel ◽

Stroke Severity ◽

Large Vessel Occlusion ◽

Time Intervals ◽

Vessel Occlusion ◽

Before And After ◽

Transferred Patients ◽

Stroke Center

BackgroundEvidence of the consequences of different prehospital pathways before mechanical thrombectomy (MT) in large vessel occlusion stroke is inconclusive. The aim of this study was to investigate the infarct extent and progression before and after MT in directly admitted (mothership) versus transferred (drip and ship) patients using the Alberta Stroke Program Early CT Score (ASPECTS).MethodsASPECTS of 535 consecutive large vessel occlusion stroke patients eligible for MT between 2015 to 2019 were retrospectively analyzed for differences in the extent of baseline, post-referral, and post-recanalization infarction between the mothership and drip and ship pathways. Time intervals and transport distances of both pathways were analyzed. Multiple linear regression was used to examine the association between infarct progression (baseline to post-recanalization ASPECTS decline), patient characteristics, and logistic key figures.ResultsASPECTS declined during transfer (9 (8–10) vs 7 (6-9), p<0.0001), resulting in lower ASPECTS at stroke center presentation (mothership 9 (7–10) vs drip and ship 7 (6–9), p<0.0001) and on follow-up imaging (mothership 7 (4–8) vs drip and ship 6 (3–7), p=0.001) compared with mothership patients. Infarct progression was significantly higher in transferred patients (points lost, mothership 2 (0–3) vs drip and ship 3 (2–6), p<0.0001). After multivariable adjustment, only interfacility transfer, preinterventional clinical stroke severity, the degree of angiographic recanalization, and the duration of the thrombectomy procedure remained predictors of infarct progression (R2=0.209, p<0.0001).ConclusionsInfarct progression and postinterventional infarct extent, as assessed by ASPECTS, varied between the drip and ship and mothership pathway, leading to more pronounced infarction in transferred patients. ASPECTS may serve as a radiological measure to monitor the benefit or harm of different prehospital pathways for MT.

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Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial

Stroke ◽

10.1161/strokeaha.120.033806 ◽

2021 ◽

Author(s):

Shadi Yaghi ◽

Eytan Raz ◽

Seena Dehkharghani ◽

Howard Riina ◽

Ryan McTaggart ◽

...

Keyword(s):

Ischemic Stroke ◽

Infarct Volume ◽

Interquartile Range ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Endovascular Thrombectomy ◽

Post Hoc Analysis ◽

Consumption Rates ◽

Post Hoc

Background and Purpose: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (T max ) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for T max delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. Methods: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume–baseline core infarct volume)/(T max 6 or 10 s volume–baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. Results: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%–87.7%) versus 5.3% (1.1%–14.6%) of penumbral tissue was consumed based on T max >6 s ( P <0.001). In the same comparison for T max >10 s, we saw a difference of 165.4% (interquartile range, 56.1%–479.8%) versus 25.7% (interquartile range, 3.2%–72.1%; P <0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on T max >6 s ( P =0.52) or T max >10 s ( P =0.92). Conclusions: Among extended window endovascular thrombectomy patients, T max >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the T max >6-s mismatch volume may remain viable in untreated patients at 24 hours.

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Abstract 31: Penumbra Consumption Rates Based on T Max Delay and Reperfusion Status: A Post-Hoc Analysis of the Defuse-3 Trial

Stroke ◽

10.1161/str.52.suppl_1.31 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Shadi Yaghi ◽

Eytan Raz ◽

Seena Dehkharghani ◽

Howard Riina ◽

Ryan McTaggart ◽

...

Keyword(s):

Infarct Volume ◽

Secondary Analysis ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Consumption Rates ◽

Definition Of ◽

Post Hoc ◽

New Generation

Introduction: In patients with acute large vessel occlusion, the definition of penumbral tissue based on T max delay perfusion imaging is not well established in relation to late-window endovascular thrombectomy (EVT). In this study, we sought to evaluate penumbra consumption rates for T max delays in patients treated between 6 and 16 hours from last known normal. Methods: This is a secondary analysis of the DEFUSE-3 trial, which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6-16 hours of last known normal. The primary outcome is percentage penumbra consumption defined as (24 hour infarct volume-core infarct volume)/(Tmax volume-baseline core volume). We stratified the cohort into 4 categories (untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates. Results: We included 143 patients, of which 66 were untreated, 16 had TICI 0-2a, 46 had TICI 2b, and 15 had TICI 3. In untreated patients, a median (IQR) of 48% (21% - 85%) of penumbral tissue was consumed based on Tmax6 as opposed to 160.6% (51% - 455.2%) of penumbral tissue based on Tmax10. On the contrary, in patients achieving TICI 3 reperfusion, a median (IQR) of 5.3% (1.1% - 14.6%) of penumbral tissue was consumed based on Tmax6 and 25.7% (3.2% - 72.1%) of penumbral tissue based on Tmax10. Conclusion: Contrary to prior studies, we show that at least 75% of penumbral tissue with Tmax > 10 sec delay can be salvaged with successful reperfusion and new generation devices. In untreated patients, since infarct expansion can occur beyond 24 hours, future studies with delayed brain imaging are needed to determine the optimal T max delay threshold that defines penumbral tissue in patients with proximal anterior circulation large vessel occlusion.

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Abstract P485: Predictors and Clinical Impact of Deep Grey Matter Infarction After Endovascular Treatment for Large Vessel Occlusion Stroke: Results From the Escape-NA1 Trial

Stroke ◽

10.1161/str.52.suppl_1.p485 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Johanna Ospel ◽

Michael D Hill ◽

Nima Kashani ◽

Arnuv Mayank ◽

Nishita Singh ◽

...

Keyword(s):

Grey Matter ◽

Infarct Volume ◽

Multivariable Analysis ◽

Diffusion Weighted Mri ◽

Vessel Occlusion ◽

Lentiform Nucleus ◽

Good Outcome ◽

Deep Grey Matter ◽

Post Hoc

Purpose: In this post-hoc analysis of the ESCAPE-NA1 trial, we investigated the prevalence of deep grey matter infarcts and their influence on clinical outcome. Methods: Infarcts on 24 hour follow up imaging (non contrast head CT or diffusion-weighted MRI) were categorized as predominantly deep grey matter infarcts (caudate and/or lentiform nucleus infarcts with sparing of the superficial grey matter and white matter) vs. other infarcts. Total infarct volume was manually segmented in all patients. When MRI follow-up was available, deep grey matter and grey matter infarct volumes were segmented separately. Multivariable logistic regression with adjustment for key minimization variables and by infarct volume was used to assess the association of predominantly deep grey matter infarcts and good outcome. Results: Of the 1026 included patients, 316 (30.8%) had predominantly deep grey matter infarcts. Cumulative proportions of good outcome for overall, grey matter, deep grey matter, and superficial grey matter infarct volumes are shown in the figure. Good outcomes were more frequently achieved in patients with predominantly deep grey matter infarcts (239/316 [75.6%] vs. 374/704 [53.1%]). Deep infarcts were tightly correlated with infarct volume (Pearson rho -0.35) and in multivariable analysis deep grey matter infarcts were predictive of outcome overall; when examined in volume percentiles, there was no effect of deep infarct location. Conclusion: Predominantly deep grey matter infarcts are associated with good outcomes. Deep grey matter infarct location favorable prognosis is associated with small overall infarct size.

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Abstract WP367: Effect of Early Blood Pressure Reduction on Infarct Size in Patients With Large Vessel Occlusion

Stroke ◽

10.1161/str.51.suppl_1.wp367 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

David Baker ◽

Dinesh Jillella ◽

Takashi Shimoyama ◽

Ken Uchino

Keyword(s):

Magnetic Resonance Imaging ◽

Blood Pressure ◽

Infarct Size ◽

Collateral Circulation ◽

Infarct Volume ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Resonance Imaging ◽

Vessel Occlusion ◽

Significant Drop

Introduction: In patients with large vessel occlusion presenting with acute ischemic stroke, cerebral perfusion is a major determinant of stroke severity. However, limited data exists to guide hemodynamic management of these patients early after presentation. In this study, we aim to evaluate the effect of blood pressure reductions during the hyper-acute period on infarct size. Methods: From a clinical stroke registry at a single comprehensive stroke center, we reviewed patients with middle cerebral artery (M1) or internal carotid artery occlusion who underwent hyperacute magnetic resonance imaging (MRI) for endovascular treatment decision in 2018. Infarct volume was determined by area of reduced apparent diffusion coefficient using RAPID software. Collateral circulation was scored based on baseline CT angiogram (good collaterals constituted >50% filling, poor collaterals ≤50% filling). Average mean arterial pressure (MAP) readings from the first hour of presentation were compared to average MAP readings from the hour prior to magnetic resonance imaging. For the purposes of our study, a drop of > 20% in the average MAP was regarded as a significant decrease. We hypothesized that both significant drop in MAP and the presence of good collateral circulation were independent predictors of infarct volume expressed as a logarithmic value in multivariable regression model. Results: Of the 35 patients (mean age 67, mean NIHSS 16) meeting inclusion criteria, 11% of patients experienced an early significant drop in MAP prior to time of MRI. Among patients with a significant drop in MAP, the average decrease was 35 mm Hg ±3.3 among those with significant drop from a baseline mean MAP of 125 mm Hg. In the multivariable analysis adjusting for collateral status, a significant drop in average MAP was independently associated with an increase in infarct volume (β = -0.727, p=0.0306). Collateral status also independently predicted infarct size (β=0.775, p=0.0007). Conclusion: Among ischemic stroke patients with large vessel occlusion, a >20% drop in MAP during the hyper-acute period is associated with larger infarct volumes. Further studies are needed to optimize early blood pressure management in these patients.

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Abstract T P26: Combining Clinical and Imaging Data to Develop a Highly Predictive Model of Outcomes in the MR RESCUE Trial

Stroke ◽

10.1161/str.46.suppl_1.tp26 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Chelsea S Kidwell ◽

Reza Jahan ◽

Jeffrey Gornbein ◽

Jeffry R Alger ◽

Val Nenov ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Patient Characteristics ◽

Hemorrhagic Transformation ◽

Imaging Data ◽

Vascular Events ◽

Vessel Occlusion ◽

Intermediate Variables ◽

Core Volume

Background: Identifying patient characteristics that predict outcomes in acute ischemic stroke may assist in triaging those who are candidates for endovascular therapies. We sought to identify predictors of outcome in the overall Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohort and compare results to the previously validated Totaled Health Risks in Vascular Events (THRIVE) score. Methods: MR RESCUE randomized 118 acute ischemic stroke patients with multimodal imaging to embolectomy or standard care within 8 hours of onset. For this analysis, we investigated 17 baseline variables (e.g. age, predicted core volume, time to enrollment) and 8 intermediate variables (e.g. hemorrhagic transformation, day 7 recanalization, final infarct volume) with the potential to impact outcomes (day 90 mRS). The baseline variables were analyzed employing bivariate and multivariate methods (random forest and logistic regression). Two models were developed, one including only significant baseline variables, and the second also incorporating significant intermediate variables. Results: A multivariate model (Table) employing only baseline covariates achieved an overall accuracy (C statistic) of 85% in predicting poor outcome (day 90 mRS 3-6) compared to 80.5% for the THRIVE score. A second model (Table) adding significant intermediate variables achieved 89% accuracy in predicting day 90 mRS. Conclusions: In the MR RESCUE trial, advanced imaging variables, including predicted core volume and site of vessel occlusion, contributed to a highly accurate multivariable model of outcome. In the development phase, this model achieved higher accuracy than the THRIVE score. Future studies are needed to validate this model in an independent cohort.

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Abstract TP239: Cross-Training In-Hospital Operating Staff Significantly Improves Door-to-Puncture Time in Thrombectomy Patients

Stroke ◽

10.1161/str.51.suppl_1.tp239 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Angela M Callahan ◽

Axel Rosengart ◽

Karissa Graham ◽

Kellie Capone ◽

Kathryn Wright ◽

...

Keyword(s):

Operating Room ◽

Patient Characteristics ◽

Reperfusion Therapy ◽

Functional Independence ◽

Stroke Severity ◽

Fisher Exact Test ◽

Large Contribution ◽

Chi Square ◽

Exact Test ◽

Significant Difference

Objective: Delay in endovascular reperfusion in patients with acute large-vessel cerebral occlusion decreases the likelihood of functional independence. Given the large contribution of the pre-puncture, in-hospital time period to the overall speed of reperfusion therapy we evaluated the benefits and impediments of utilizing an immediately available OR team to reduce door-to-puncture time compared to a traditional model of an on-call team. Methods: Prospectively collected data were retrospectively analyzed to compare the readiness strategies of 2 comprehensive stroke centers of the Geisinger Health System serving stroke patients in rural and suburban Pennsylvania with different hospital level characteristics: Center A with an in-hospital available operating room team cross-trained in both operating and neuroendovascular procedures and center B with a dedicated on-call neuroendovascular team. Data compared included patient demographics and presentation characteristics, stroke severity, door-to-puncture time, and successful reperfusion ( t test, Fisher exact test, Chi square test). Results: There was no significant difference in the baseline stroke patient characteristics at center A (n=31) and center B (n= 45): 61% vs. 62% females; mean age 72 (range 47 to 93) vs. 69 (range 28 to 96) (p=0.35); admission NIHSS 17 vs 17, respectively. Successful reperfusion (TICI 2b-3) was achieved in 98% and 97% of cases in center A and B, respectively (p=0.79) but door-to-puncture time differed significantly between 50 in center A compared to 121 minutes in center B (58% reduction, p<0.02). Conclusion: Crossed-training in-hospital operating room staff in neuroendovascular procedures significantly reduces door-to-puncture time in thrombectomy patients when compared to a traditional on-call neuroendovascular call team. Based on existing data, this achievement in earlier reperfusion is expected to translate directly to improve clinical outcome.

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Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation

Frontiers in Neurology ◽

10.3389/fneur.2021.661955 ◽

2021 ◽

Vol 12 ◽

Author(s):

Elena Spronk ◽

Gina Sykes ◽

Sarina Falcione ◽

Danielle Munsterman ◽

Twinkle Joy ◽

...

Keyword(s):

Ischemic Stroke ◽

Immune System ◽

Reperfusion Therapy ◽

Hemorrhagic Transformation ◽

Stroke Severity ◽

Mortality Factors ◽

Increased Risk ◽

Relationship Of ◽

The Relationship

Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. It occurs when peripheral blood extravasates across a disrupted blood brain barrier (BBB) into the brain following ischemic stroke. Preventing HT is important as it worsens stroke outcome and increases mortality. Factors associated with increased risk of HT include stroke severity, reperfusion therapy (thrombolysis and thrombectomy), hypertension, hyperglycemia, and age. Inflammation and the immune system are important contributors to BBB disruption and HT and are associated with many of the risk factors for HT. In this review, we present the relationship of inflammation and immune activation to HT in the context of reperfusion therapy, hypertension, hyperglycemia, and age. Differences in inflammatory pathways relating to HT are discussed. The role of inflammation to stratify the risk of HT and therapies targeting the immune system to reduce the risk of HT are presented.

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Similar admission NIHSS may represent larger tissue-at-risk in patients with right-sided versus left-sided large vessel occlusion

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-017785 ◽

2021 ◽

pp. neurintsurg-2021-017785

Author(s):

Adrian Mak ◽

Charles Matouk ◽

Emily W Avery ◽

Jonas Behland ◽

Dietmar Frey ◽

...

Keyword(s):

At Risk ◽

Multivariate Analysis ◽

Linear Models ◽

Infarct Volume ◽

Large Vessel ◽

Stroke Severity ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Nihss Score ◽

Clinical Biomarker

BackgroundWe investigated the effects of the side of large vessel occlusion (LVO) on post-thrombectomy infarct volume and clinical outcome with regard to admission National Institutes of Health Stroke Scale (NIHSS) score.MethodsWe retrospectively identified patients with anterior LVO who received endovascular thrombectomy and follow-up MRI. Applying voxel-wise general linear models and multivariate analysis, we assessed the effects of occlusion side, admission NIHSS, and post-thrombectomy reperfusion (modified Thrombolysis in Cerebral Infarction, mTICI) on final infarct distribution and volume as well as discharge modified Rankin Scale (mRS) score.ResultsWe included 469 patients, 254 with left-sided and 215 with right-sided LVO. Admission NIHSS was higher in those with left-sided LVO (median (IQR) 16 (10–22)) than in those with right-sided LVO (14 (8–16), p>0.001). In voxel-wise analysis, worse post-thrombectomy reperfusion, lower admission NIHSS score, and poor discharge outcome were associated with right-hemispheric infarct lesions. In multivariate analysis, right-sided LVO was an independent predictor of larger final infarct volume (p=0.003). There was a significant three-way interaction between admission stroke severity (based on NIHSS), LVO side, and mTICI with regard to final infarct volume (p=0.041). Specifically, in patients with moderate stroke (NIHSS 6–15), incomplete reperfusion (mTICI 0–2b) was associated with larger final infarct volume (p<0.001) and worse discharge outcome (p=0.02) in right-sided compared with left-sided LVO.ConclusionsWhen adjusted for admission NIHSS, worse post-thrombectomy reperfusion is associated with larger infarct volume and worse discharge outcome in right-sided versus left-sided LVO. This may represent larger tissue-at-risk in patients with right-sided LVO when applying admission NIHSS as a clinical biomarker for penumbra.

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