DAWN Trials Research Articles

Is time really brain in stroke therapy?: A meta-analysis of mechanical thrombectomy up to 155h post ictus.

Mechanicalthrombectomy (MT) has been established as the gold standard of treatment for patients with Acute Ischemic Stroke (AIS) who present up to 6h after the onset of the stroke. Recently, the DEFUSE-3 and DAWN trials established the safety of starting the MT procedure up to 16 and 24h after the patient was last seen well, respectively. The purpose of this study is to assess the safety and functional effects of thrombectomy in individuals with AIS detected at a late stage (> 24h). PubMed, Web of Science, Embase, and Cochrane databases were thoroughly searched for research on MT in patients in the extremely late time window after AIS. The primary outcomes were symptomatic cerebral hemorrhage, 90-day mortality, Thrombolysis in Cerebral Infarction (TICI) 2b-3, and Modified Rankin Scale (mRS) 0-2. Our study included fifteen studies involving a total of 1,221 patients who presented with AIS and an extended time window. The primary outcome of interest was the favorable functional outcome, mRS 0-2 at 90days. The pooled proportion for this outcome was 45% (95% confidence interval 34-58%). Other outcomes included the TICI 2b or 3 (successful recanalization), which was reported in 12 studies and had a 79% incidence in the study population (95% CI 68-87%). Complications included: symptomatic intracranial hemorrhage (sICH), which revealed an incidence of 7% in the study population (95% CI 5-10%); and 90-day mortality, which reported a 27% incidence (95% CI 24-31%). In addition, we conducted a comparative analysis between endovascular treatment and standard medical therapy. Our meta-analysis provides evidence that supports the need of further randomized and prospective clinical trials to better assess the effectiveness and safety of MT in these patients.

Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.

Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24weeks followed by an open-label phase of 28weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24weeks was more with dorzagliatin with an estimated treatment difference of -0.57% in the SEED trial and -0.66% in the DAWN trial. The desired glycosylated hemoglobin (<7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diabetes are needed to comment upon the long-term therapeutic performance of dorzagliatin. Likewise, evidence needs to be generated from other countries, patients with organ dysfunction, a history of severe hypoglycemia, cardiac diseases, and elderly patients before extending the use of dorzagliatin. Apart from monitoring lipid profiles, long-term safety studies of dorzagliatin should involve the assessment of serum uric acid, lactate, renal function, liver function, and cardiovascular parameters.

Abstract WP193: Endovascular Thrombectomy for DAWN- and DEFUSE 3 Ineligible Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis

Background: The current evidence supports the benefits of endovascular treatment (EVT) in acute ischemic stroke (AIS) with large vessel occlusion (LVO). The DAWN and DEFUSE-3 trials expanded the EVT window up to 24 hours. A few real-world studies explored EVT outcomes in DAWN/DEFUSE-3 ineligible (NDND) patients. Methods: This meta-analysis investigated EVT outcomes in patients with late-window anterior circulation LVO, including both DAWN/DEFUSE-3 eligible (DD) and NDND patients. Nine studies were included, focusing on study characteristics, risk of bias, and outcomes. Results: Baseline characteristics showed comparable age, gender, comorbidities, NIHSS score, and ASPECTS between DD and NDND patients. NDND patients exhibited larger infarct volumes and higher atrial fibrillation rate. Successful reperfusion rates (TICI 2b-3) were comparable between the two groups (OR= 0.86; 95% CI= 0.40, 1.84; p = 0.689), with significant heterogeneity (I 2 = 73%; P = 0.002). Functional independence (90-day mRS score 0-2) was not significantly different between the two groups (OR= 1.12; 95% CI= 0.77, 1.63; p = 0.552) with notable heterogeneity (I 2 = 46%, p = 0.063). Symptomatic intracranial hemorrhage (sICH) rate was lower in the DD group as compared to NDND patients (OR= 0.49; 95% CI= 0.25, 0.93; p = 0.029) with no heterogeneity (I 2 = 0%, p = 0.552). 90-day mortality was lower in the DD group than in the NDND group (OR= 0.55; 95%-CI= 0.37, 0.82; p = 0.004) with no significant heterogeneity (I 2 = 0%, p = 0.536). Conclusion: While this meta-analysis showed comparable rates of functional independence between DD and NDND patients, the potential bias introduced by the higher rates of sICH and mortality in the latter group should prompt great care when offering EVT to NDND patients. Less restricted EVT eligibility criteria might yield positive outcomes in real-world practice in specific patients. However, increased risks of sICH and mortality in NDND patients warrant further investigation to optimize the risk-benefit balance in expanding EVT eligibility criteria.

Endovascular treatment versus no endovascular treatment after 6–24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial

Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]). In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow. Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Mechanical thrombectomy for large vessel occlusion between 6 and 24 h: outcome comparison of DEFUSE-3/DAWN eligible versus non-eligible patients.

The DEFUSE-3 and DAWN trials showed that mechanical thrombectomy (MT) improves the outcome of selected patients with anterior circulation large vessel occlusions (LVO) up to 24 h after stroke onset. However, it is unknown whether only those patients fulfilling the trial inclusion criteria benefit, or whether benefit is seen in a broader range of patients presenting between 6 and 24 h. We determined whether fulfilling the DEFUSE-3 and DAWN selection criteria affects outcomes in MT patients in clinical practice. We reviewed adult patients with LVO treated with MT between 6 and 24 h after stroke onset at five Swiss stroke centers between 2014 and 2021. We compared two groups: (1) patients who satisfied neither DEFUSE-3 nor DAWN criteria (NDND) and (2) those who satisfied DEFUSE-3 or DAWN criteria (DOD). We used logistic regression to examine the impact of trial eligibility on two safety outcomes (symptomatic intracranial hemorrhage [sICH] and all-cause mortality at 3 months) and two efficacy outcomes (modified Rankin Score [mRS] shift toward lower categories and mRS of 0-2 at 3 months). Of 174 patients who received MT, 102 (59%) belonged to the NDND group. Rates of sICH were similar between the NDND group and the DOD group (3% vs. 4%, p = 1.00). Multivariable regression revealed no differences in 3-month all-cause mortality (aOR 2.07, 95% CI 0.64-6.84, p = 0.23) or functional outcomes (mRS shift: acOR 0.81, 95% CI 0.37-1.79, p = 0.60; mRS 0-2: aOR 0.91, 95% CI 0.31-2.57, p = 0.85). Among adult patients with LVO treated with MT between 6 and 24 h, safety and efficacy outcomes were similar between DEFUSE-3/DAWN eligible and ineligible patients. Our data provide a compelling rationale for randomized trials with broader inclusion criteria for MT.

Multiparametric Neuroimaging and Its Association with Non-Contrast Computed Tomography in Late-Window Large Vessel Occlusion Acute Stroke

Introduction: Endovascular treatment (EVT) for acute ischemic stroke (AIS) between 6 and 24 h is established as a standard of care among patients selected by multiparametric neuroimaging. We aimed to explore neuroimaging parameters in late-window large vessel occlusion (LVO) patients and its association with non-contrast computed tomography (NCCT) findings. Methods: We included consecutive AIS patients within 6–24 h from the symptoms onset with LVO. We described multiparametric imaging findings, the rate of patients who fulfilled imaging perfusion criteria according to the DAWN and DEFUSE-3 trials that define the computed tomography perfusion mismatch (CTP-MM) group and its association with NCCT focused on Alberta Stroke Program Early CT Score (ASPECTS). We also analyzed the association between neuroimaging parameters and the clinical outcome determined by the 90-day modified Rankin scale (mRS). Results: We included 206 patients, of them, 176 (85.4%) presented CTP-MM and 184 (89.3%) presented an ASPECTS ≥6 on admission. The rate of CTP-MM was 90.8% in patients with ASPECTS ≥6, compared with 40.9% in those with low ASPECTS. ASPECTS was moderately correlated with ischemic core determined by cerebral blood flow <30% volume (rS = −0.557, p < 0.001). In EVT-treated patients (185, 89.8%), after adjusting for identifiable confounders, the presence of CTP-MM was a predictor of 90-day functional independence (OR: 3.38; 95% CI: 1.01–11.29; p = 0.048). We did not find an association between CTP-MM and 90-day functional disability (ordinal mRS shift, aOR: 1.39; 95% CI: 0.58–3.34; p = 0.459). Conclusions: A great majority of patients who presented a LVO in the late window fulfilled guidelines imaging criteria to undergo EVT, especially those with high ASPECTS (≥6). Our data suggest that NCCT with CT angiography could be a reasonable approach for AIS treatment selection also in the late window.

Endovascular treatments for ischemic stroke

Highlights. Mechanical thrombectomy is the “gold standard” treatment of patients with large-vessel occlusions. Five randomized trials conducted in 2015 made a significant contribution to the development and introduction of mechanical thrombectomy into clinical practice. The DAWN and DEFUSE-3 trials have provided new insights into the pathophysiology of ischemic stroke and ensured the advancement in the therapeutic field.Abstract. Stroke is one of the leading causes of death and disability worldwide. The general strategy for the treatment of ischemic stroke is aimed at restoring blood flow to the ischemic regions of the brain. Intravenous thrombolysis has been the treatment for acute ischemic stroke since 1996. However, since 2015, as a result of 5 randomized trials, endovascular mechanical thrombectomy has become the gold standard for the treatment of patients with large cerebral artery occlusion. The DAWN and DEFUSE 3 trials have provided new insights into the pathophysiology of ischemic stroke, shifting the paradigm from “time = brain” to “collaterals = brain”. In this article, the authors will consider development of endovascular devices, modern mechanical thrombectomy techniques, and directions for further research of endovascular treatment for ischemic stroke.

Abstract WP99: One-stop Stroke Mangement: Core And Hypoperfusion Maps From Multiphase Flat-panel Ct

Introduction: Acute ischemic stroke (AIS) patients transferred directly to the interventional suite can undergo flat-panel CT (FPCT) to bypass multidetector CT (MDCT) and eliminate delays to reperfusion therapy. However, the diagnostic adequacy of FPCT needs to be corroborated prior to eliminating MDCT from stroke care pathways. CT perfusion (CTP) maps played an important role in assessing infarcted vs. hypoperfused cerebral tissue in the 6-24 hour time window in the DAWN and DEFUSE-3 trials. We evaluated the diagnostic accuracy of FPCTP to identify infarcted vs. hypoperfused tissue using MDCTP as a reference. Materials and Methods: Between Oct. 19 and Nov. 21, 16 AIS patients at a tertiary urban hospital underwent FPCT and FPCTP. IRB approval and informed written consent was obtained. Ten patients underwent CTP in the ED. FPCTP was obtained using a Siemens Artis Q Biplane system. Data was post-processed on a separate prototype workstation, allowing visualization of ten 3D volumes in different phases of contrast enhancement (colored), and perfusion maps (CBF, CBV, MTT, TTP, T max , and TTD) (Figure 1). The CBF and T max , volumes have been further processed to generate color-coded hypoperfusion and core maps. Results: Eight FPCTP acquisitions were excluded due to technical problems, no available CTP, or severe motion artifacts. The infarcted and hypoperfused regions identified on FPCTP qualitatively agree with the regions identified on MDCTP. The time between CTP and FPCTP scans was a mean of 1h 2min (± 34min, 40- 2h30min). Three patients were under GA, the remaining 5 patients were scanned under moderate sedation. Three patients received IV-rtPA. Conclusion: FPCTP can be acquired to generate CBF, CBV, MTT, TTP, T max , and TTD maps in the interventional suite, potentially bypassing MDCTP and eliminating delays to reperfusion therapy. Quantitative results require advanced post-processing, particularly for artifact mitigation. The study is limited by the small sample size.

Editors' Note: Association of Initial Imaging Modality and Futile Recanalization After Thrombectomy

In “Association of Initial Imaging Modality and Futile Recanalization After Thrombectomy,” Meinel et al. reported that the rate of futile recanalization (defined as 90-day modified Rankin Scale (mRS) score 4–6 despite successful recanalization) among patients enrolled in the BEYOND-SWIFT multicenter, retrospective observational registry was significantly higher in patients selected for thrombectomy based on a CT scan as compared with patients selected for thrombectomy based on an MRI. Siegler and Thon cautioned that these findings should not dissuade against (1) use of a CT scan to determine eligibility for thrombectomy because this could lead to unnecessary delays in care or (2) performance of thrombectomy after CT scans because the imaging modality itself does not directly affect outcome and 40% of patients selected for thrombectomy based on a CT scan had a good 90-day mRS score (which represents a 22%–27% absolute increase compared with patients treated with medical management in the DAWN and DEFUSE-3 trials). Meinel et al agreed that it is imperative to avoid delays before thrombectomy and reinforced that their findings should not influence the selection of imaging modality for potential thrombectomy candidates. They also pointed out that implementation of high-speed MRI protocols should be considered to obtain more detailed information than a CT scan can provide while avoiding lengthy delays between imaging and groin puncture. In “Association of Initial Imaging Modality and Futile Recanalization After Thrombectomy,” Meinel et al. reported that the rate of futile recanalization (defined as 90-day modified Rankin Scale (mRS) score 4–6 despite successful recanalization) among patients enrolled in the BEYOND-SWIFT multicenter, retrospective observational registry was significantly higher in patients selected for thrombectomy based on a CT scan as compared with patients selected for thrombectomy based on an MRI. Siegler and Thon cautioned that these findings should not dissuade against (1) use of a CT scan to determine eligibility for thrombectomy because this could lead to unnecessary delays in care or (2) performance of thrombectomy after CT scans because the imaging modality itself does not directly affect outcome and 40% of patients selected for thrombectomy based on a CT scan had a good 90-day mRS score (which represents a 22%–27% absolute increase compared with patients treated with medical management in the DAWN and DEFUSE-3 trials). Meinel et al agreed that it is imperative to avoid delays before thrombectomy and reinforced that their findings should not influence the selection of imaging modality for potential thrombectomy candidates. They also pointed out that implementation of high-speed MRI protocols should be considered to obtain more detailed information than a CT scan can provide while avoiding lengthy delays between imaging and groin puncture.

The algorithm of reperfusion treatment of the ischemic stroke: focus on DAWN and DEFUSE-3 trials

The history of reperfusion treatment for ischemic stroke was officially recognized in 1996, when the use of systemic thrombolytic therapy (TLT) was authorized in the United States of America and the first clinical guidelines were published (American Heart Association (AHA) Stroke Council). The use of TLT for the treatment of ischemic stroke in the Russian Federation began in 2005–2006. The next step was the development of endovascular reperfusion techniques (2005) following the presentation of the results of the MERCI study, which evaluated the safety and efficacy of microconductors for fragmentation and destruction of blood clots. Currently, neurologists working with patients with acute cerebrovascular accidents are guided by national regulatory documents — order of the Ministry of Health of the Russian Federation dated by November 15, 2012 No. 928n “On approval of the Procedure for providing medical care to patients with acute cerebrovascular accidents” and the Protocol of reperfusion therapy acute ischemic stroke (2019), which provide basic information on the methods of diagnosis and treatment of ischemic cerebral stroke, as well as international recommendations ESO, AHA/ASA, which provide grounds for increasing therapeutic options, in particular by extending the time of the “therapeutic window”. The authors of article created the algorithm for reperfusion therapy for ischemic stroke, based on the analysis and generalization of regulatory documents, clinical guidelines and the results of DAWN and DEFUSE-3 studies.

Abstract P468: Functional Outcome of Patients Undergoing Mechanical Thrombectomy Outside of the Dawn and Defuse Criteria

Background: The DAWN and DEFUSE trials (D&amp;D) extended the mechanical thrombectomy (MT) window to 16-24 hours from last known normal (LKN) in patients with internal carotid artery (ICA) or proximal middle cerebral artery (M1) large vessel occlusions (LVO), with limits on core infarct and penumbra size. With advances in imaging and procedural techniques, many have extended these results to patients outside of the study criteria, yet there is limited analysis of outcomes in those receiving MT beyond these guidelines. This study evaluates the functional outcome of MT in acute stroke patients presenting within 24 hours of LKN outside of the D&amp;D criteria vs those meeting study criteria at a single Comprehensive Stroke Center. Methods: An IRB approved study was performed in which consecutive anterior circulation ischemic stroke patients presenting to Wake Forest Baptist Health from 12/1/18-12/31/19 within 0-24 hours of LKN were retrospectively studied. Patients were grouped by eligibility for DAWN or DEFUSE (mRS ≦1, ICA/M1 occlusion, age &lt;80 NIHSS ≧10 and core 0-30, or age &lt;80 NIHSS ≧20 and core 31-51, or age ≧80 NIHSS ≧10 and core 0-20; or mRS ≦2, NIHSS ≧6, ICA/M1 occlusion with core &lt;70, mismatch volume &gt;15, and mismatch ratio &gt;1.8) or neither. Good outcome was defined as mRS ≦3 within 3 months of discharge. If not available, discharge mRS was used. A multivariate logistic regression model analyzed the outcome controlling for confounding factors. Results: Of 130 patients, 57 (44%) fell outside D&amp;D criteria. There was no significant difference between age, rate of IV tPA, admission NIHSS, baseline co-morbidities, or core infarct size between groups. Median mismatch volume was greater in the D&amp;D group compared to patients in the non D&amp;D group (97cc, IQR 67-146 vs 67cc, IQR 30-111; p=0.002). Good outcome was seen in 34 (47%) D&amp;D patients vs 30 (53%) in the non D&amp;D group; controlling for confounding factors affecting 3 month mRS (age, NIHSS, time to revascularization, atrial fibrillation, prior stroke), this was not statistically significant (p=0.25). Conclusion: The outcome of MT in patients with anterior circulation LVO is not different between those meeting and not meeting D&amp;D criteria. MT should be considered in patients presenting within 24 hours outside study guidelines.

Abstract P272: Management of Acute Stroke Patients in the Extended Window in a Large Community Cohort

Background: Published data suggest that treating qualified acute strokes within the extended window (EW) or 6-24 hours of last seen normal with endovascular therapy (EST) is associated with better 90-day outcome. In a real-world multi-ethnic practice setting, we assessed our experience in triaging and treating patients in the EW. Methods: In 2016, our system of care launched a telestroke program for 19 primary and 2 comprehensive stroke centers to include immediate video evaluation by a stroke neurologist. In 2018, screening in the EW began. If the patient met clinical criteria (baseline independence and initial NIHSS ≥ 6), neuroimaging was performed to assess for a large vessel occlusion (LVO). Referral for EST was made for patients with an LVO and appropriate CT perfusion criteria. Our study included all health plan members presenting within the EW in 2019. Assessment included demographics, NIHSS, neuroimaging data, LVO, discharge outcomes, 90-day mRS and mortality with 95% confidence interval. Results: In 2019, there were 5349 suspected strokes (1255 EW) evaluated by teleneurologists; 2130 (39.8%) patients were appropriate for acute stroke imaging workup. Of 2130, final study cohort included 388 (18.2%) EW patients who met clinical criteria and underwent neuroimaging workup, and 117 of these patients (30.2%) had an LVO. There were 57 (14.7%) meeting CT perfusion criteria and referred for EST. Compared to 331 who were not referred for EST, the 57 patients were older and more likely to have atrial fibrillation, higher NIHSS, and to be discharged to a short-term facility than home. The 51 patients who went for EST within our system had 90-day good (mRS 0-2), bad (mRS 5-6), and mortality rates comparable to those from DAWN and DEFUSE-3 trials [Table]. Conclusions: In our system, only a small proportion of suspected strokes met criteria for EST during the EW. It was possible in a community setting to achieve 90-day outcomes that were comparable to those from clinical trials.

Imaging criteria across pivotal randomized controlled trials for late window thrombectomy patient selection

BackgroundThe DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion...

Refined Ischemic Penumbra Imaging with Tissue pH and Diffusion Kurtosis Magnetic Resonance Imaging.

Imaging has played a vital role in our mechanistic understanding of acute ischemia and the management of acute stroke patients. The most recent DAWN and DEFUSE-3 trials showed that endovascular therapy could be extended to a selected group of late-presenting stroke patients with the aid of imaging. Although perfusion and diffusion MRI have been commonly used in stroke imaging, the approximation of their mismatch as the penumbra is oversimplified, particularly in the era of endovascular therapy. Briefly, the hypoperfusion lesion includes the benign oligemia that does not proceed to infarction. Also, with prompt and effective reperfusion therapy, a portion of the diffusion lesion is potentially reversible. Therefore, advanced imaging that provides improved ischemic tissue characterization may enable new experimental stroke therapeutics and eventually further individualize stroke treatment upon translation to the clinical setting. Specifically, pH imaging captures tissue of altered metabolic state that demarcates the hypoperfused lesion into ischemic penumbra and benign oligemia, which remains promising to define the ischemic penumbra's outer boundary. On the other hand, diffusion kurtosis imaging (DKI) differentiates the most severely damaged and irreversibly injured diffusion lesion from the portion of diffusion lesion that is potentially reversible, refining the inner boundary of the penumbra. Altogether, the development of advanced imaging has the potential to not only transform the experimental stroke research but also aid clinical translation and patient management.

Abstract WP75: Comparison of Automated CT Perfusion Software for Prediction of Final Infarct Volume

Introduction: CT Perfusion (CTP) has been increasingly used in patient selection for acute reperfusion therapies. Perfusion software allow for automated and faster processing using standardized approaches. We aim to compare the perfusion parameters and final infarct volume (FIV) predictability of two commercially available CTP packages (RAPID and Viz.ai). Methods: Retrospective analysis of a mechanical thrombectomy database of mechanical thrombectomy between 9/ 2018- 6/ 2019. Patients without a technically adequate baseline CTP were excluded. Ischemic core was defined as CBF&lt;30%. Patients with (1) complete post-treatment reperfusion (mTICI 2c-3) and (2) absence of parenchymal hematoma that could confound FIV calculation were used to derive the correlations between baseline core and FIV. FIV was measured on MRI (n=150) and CT (n=14). Results: A total of 164 patients were included (mean age, 66±13.14 years; baseline NIHSS, 14.93±6.73; median time from CTP to reperfusion; median 86.5 IQR [61.25-111.75] min). The median baseline rCBF&lt;30% lesion was 4.5 [0-21]cc and 10.4 [0-36]cc on Rapid and Viz.ai, respectively. There was a strong correlation across all baseline perfusion parameters: rCBF&lt;30%: R=0.813; Tmax&gt;6: R=0.879, Tmax&gt;8: R=0.866, Tmax&gt;10: R=0.852. In addition, there was a highagreement rate for binary values for qualification for the DAWN (core≤21 cc: 88.9%; ≤31cc: 82.4%; ≤51cc: 89.1%), DEFUSE-3 (93%), and EXTEND (91) trials. A total of 148 patients were fully reperfused (mTICI2c-3). Their median FIV was 23.72 [11.0-78.2] cc. There was only a marginal correlation between rCBF&lt;30% and FIV which not significantly different across the two platforms (RAPID: R=0.456; Viz.ai R=0.437, p&lt;0.001). Conclusion: The RAPID and Viz-AI software have a strong correlation in terms of the overall baseline parameters and reperfusion treatment eligibility. In fully reperfused patients, the prediction of FIV was only marginal with both softwares.

Eligibility for late endovascular treatment using DAWN, DEFUSE-3, and more liberal selection criteria in a stroke center

Background and purposeThe real-life application of DAWN and DEFUSE-3 trials has been poorly investigated. We aimed to identify the proportion of patients with acute ischemic stroke (AIS) eligible for late...

Estimating the social value of mechanical thrombectomy randomized trials on an established stroke network

BackgroundGiven the relative strength of prior mechanical thrombectomy (MT) data in face of the perceived poor natural history of emergent large vessel occlusion strokes, randomization to medical therapy during the...

233 The Impact of a Large Vessel Screening Tool to Reduce Delays in Evaluation and Intervention in Emergency Department Stroke Patients

The DAWN and DEFUSE-3 trials established endovascular thrombectomy (ET) as standard care for select patients with ischemic stroke due to large vessel occlusion (LVO) up to 24 hours from last known well (LKW). In 2018, our institution, a 600-bed Level-1 teaching hospital and Comprehensive Stroke Center with 62,000 emergency department (ED) visits per year, expanded stroke alert activation to include all patients presenting with stroke symptoms within 24 hours of LKW. However, while our volume of stroke alerts increased substantially with this stroke window expansion, the specificity of our alert process declined as many alerted patients were not eligible for neurovascular intervention. In January 2019, with the goal of improving the specificity of our stroke alert and reduce delays in treatment, we revised our stroke alert criteria to include an LVO screening tool such that patients with > 6 hours of stroke symptoms who did not have exam findings consistent with an underlying LVO did not trigger an emergent stroke alert. The vision, aphasia, and neglect (VAN) is a screening tool designed to rapidly assess for possible LVO. In 2019, we trained all emergency physicians and nurses to assess all stroke patients on arrival to the ED using the VAN screening tool. Patients with a LKW of < 6 hours or who had > 6 hours since LKW, but were VAN positive triggered a stroke alert within our facility. We then retrospectively reviewed ED stroke alert data from 2018 after we extended our stroke alert window and 2019 when we revised our stroke protocol to include the VAN tool. We compared process metrics pre- and post- intervention with our new protocol using the VAN tool. We report mean times (min) with 95% confidence interval (CI) and perform comparisons using Student’s t-tests. In 2018, our ED called 596 stroke alerts; 170 patients (30.2%) were ultimately diagnosed with ischemic stroke. January through March of 2019, 106 alerts were activated, of which 37 were diagnosed with an ischemic stroke (35%) following the implementation of our new VAN protocol. In 2018, 52 patients (8.7%) received tissue plasminogen activator (tPA) and 37 patients (6.4%) underwent ET, compared to 14 patients (13.2%) receiving tPA and 2 patients (1.9 %) undergoing ET in 2019. Mean door to alert time decreased from 18 min [16.5, 19.4] in 2018 to 13 min [6.26,11.74] in 2019 (p = 0.024). Mean treatment times decreased from door to tPA of 57.1 min [48.5, 66.1] in 2018 to 53.3. min [50.27, 56.34] in 2019 (p= 0.15), and door to groin puncture of 93.6 min [74.2, 113] in 2018 to 64 min [36.56, 91.44] in 2019 ( p> .05). Utilizing the VAN screening tool as part of our stroke alert protocol improved the overall specificity of our stroke alert. Additionally, we observed decreased door to alert, door to tPA, and door to thrombectomy times, following the implementation of our new protocol. The LVO screening tool does not appear to dramatically reduce stroke resource utilization within the ED; however, the teaching of this screening tool likely improved provider education to detect stroke symptoms and reduced delays in assessment and treatment.

Endovascular Thrombectomy for Acute Ischemic Stroke.

To review the current evidence supporting the use of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). Recent advances in AIS management by EVT have led to significant reduction in morbidity and mortality in selected patients with LVO within the anterior circulation. Until recently, use of EVT was strictly based on time criteria, within 4.5 to 12h of symptom onset with many patients presenting with "wake-up" stroke who were not considered for EVT. The positive results of the DAWN and DEFUSE-3 trials have shown benefit in extending the therapeutic window for EVT to 24 and 16h, respectively, after last known normal (LKN) time in the setting of large ischemic penumbra. These trials represent a paradigm shift in contemporary treatment of AIS, changing from a purely time-based decision to treat to an individualized decision based on clinical and radiographic findings of salvageable tissue. Overall, acute stroke management has evolved considerably over the years from intravenous thrombolysis to include EVT, with paralleled improvements in patient selection and thrombectomy devices. Since the results of the DAWN and DEFUSE-3, EVT is now considered the standard of care in select patients with anterior circulation LVO up to 24h from LKN time. Despite these developments, post-stroke disability remains pervasive and further studies are warranted in establishing the role of EVT in posterior circulation and distal vessel occlusions, with need for development of new and effective techniques for revascularization of small vessels.

Differential Benefit of Collaterals for Stroke Patients Treated with Thrombolysis or Supportive Care : APropensity Score Matched Analysis.

Leptomeningeal collaterals can slow down infarction growth; however, despite good collaterals in the DAWN and DEFUSE3 trials, outcomes were devastating if reperfusion was not attempted. The aim of this study was to compare the influence of collaterals on morphological and functional outcome in patients with acute middle cerebral artery (MCA) stroke undergoing intravenous thrombolysis (IVT) vs. supportive care (non-IVT). Out of 1639 consecutive patients examined with multiparametric computed tomography (CT) for suspected ischemic stroke, all patients with confirmed MCA stroke who did not undergo endovascular thrombectomy were selected. Propensity score matching (PSM) was used to match IVT and non-IVT treated patients for potential confounders including age, sex, National Institutes of Health Stroke Scale (NIHSS) score on admission, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion site. Regression analysis after PSM was performed to identify independent associations. After PSM, 90IVT patients were matched with 90non-IVT patients. In multivariable regression analysis, ahigh regional leptomeningeal collateral (rLMC) score was independently associated with lower final infarction volume (FIV) in the IVT group (b = -0.472, p < 0.001) but not in the non-IVT group (b = -0.116, p = 0.327). The trichotomized rLMC scores predicted functional outcome in IVT treated patients (adjusted odds ratio, aOR = 4.57, 95% confidence interval, CI, 1.03-20.32, p = 0.046) but showed no independent association with outcome in the non-IVT group (aOR = 0.69, 95% CI 0.07-6.80, p = 0.753). Good collaterals favored smaller FIV and good functional outcome in IVT treated patients but not in non-IVT treated patients. Good collateral flow may have limited prognostic value if IVT is not administered to attempt reperfusion.