Odds Of Good Functional Outcome Research Articles

Inhalational versus Intravenous General Anesthesia for mechanical thrombectomy for stroke: A single centre retrospective study

BackgroundWhen general anesthesia is used for endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), the choice of anesthetic agents for maintenance remains inconclusive. The different effects of intravenous anesthetic and volatiles agents on cerebral hemodynamics are known and may explain differences in outcomes of patients with cerebral pathologies exposed to the different anesthetic modalities. In this single institutional retrospective study, we assessed the impact of total intravenous (TIVA) and inhalational anesthesia on outcomes after EVT. MethodsWe conducted a retrospective analysis of all patients ≥ 18 years who underwent EVT for AIS of the anterior or posterior circulation under general anesthesia. Baseline patient characteristics, anesthetic agents, intra operative hemodynamics, stroke characteristics, time intervals and clinical outcome data were collected and analyzed. ResultsThe study cohort consisted of 191 patients. After excluding 76 patients who were lost to follow up at 90 days, 51 patients received inhalational anesthesia and 64 patients who received TIVA were analyzed. The clinical characteristics between the groups were comparable. Multivariate logistic regression analysis of outcome measures for TIVA versus inhalational anesthesia showed significantly increased odds of good functional outcome (mRS 0–2) at 90 days (adjusted odds ratio, 3.24; 95% CI, 1.25–8.36; p = 0.015) and a non-significant trend towards decreased mortality (adjusted odds ratio, 0.73; CI, 0.15–3.6; p = 0.70). ConclusionPatients who had TIVA for mechanical thrombectomy had significantly increased odds of good functional outcome at 90 days and a non-significant trend towards decrease in mortality. These findings warrant further investigation with large randomized, prospective trials.

Abstract WP4: Intravenous Thrombolysis And Outcomes In Patients With Large-vessel Stroke Directly Admitted Or Transferred To A Thrombectomy-capable Center

Objective: To assess whether the effect of intravenous thrombolysis in patients with large-vessel occlusion differed between patients directly admitted to thrombectomy-capable centers and patients transferred from local stroke centers without thrombectomy capabilities. Methods: We included 3206 patients with an acute ischemic large-vessel stroke with first imaging within 7 hours after onset that were directly admitted to thrombectomy-capable centers and treated with thrombectomy, or transferred from local stroke centers for thrombectomy evaluation, between 2017 and 2021 in Catalonia, Spain. Primary outcome was the degree of disability at 90 days, as evaluated by the shift analysis on the mRs score. Secondary outcomes included mortality at 90 days and the rate of parenchymal hemorrhage and successful reperfusion. Inverse-probability weighting clustered at the type of stroke center was used to estimate the effects. Results: The analysis included 2268 patients (975[49%] treated with thrombolysis) directly admitted to thrombectomy-capable centers and 938 patients (580[66%] treated with thrombolysis and 616[67%] treated with thrombectomy) transferred from local stroke centers (mean age 72±13 years, median NIHSS score 17[IQR 12-21], 1363 female[48%]). Patients treated with intravenous thrombolysis were younger, had shorter time from onset to first image acquisition, and higher rates of wake-up stroke, atrial fibrillation and anticoagulation intake. The effect of intravenous thrombolysis on the primary outcome was similar in patients directly admitted to thrombectomy-capable centers (acOR 1.50, 95% CI 1.24-1.81) and patients transferred from local stroke centers (acOR 1.44, 95% CI 1.04 to 2.01)(p interaction =0.68). Patients treated with intravenous thrombolysis had lower mortality rate, higher rate of parenchymal hematoma and similar rate of successful reperfusion, with no difference according to type of center (p interaction >0.1). Conclusion: Administration of intravenous thrombolysis in patients with a large-vessel stroke with intention to thrombectomy was associated with higher odds of good functional outcome and higher rates of parenchymal hematoma, independently of the type of stroke center were it was administered.

Intravenous Thrombolysis with Tenecteplase for the Treatment of Acute Ischemic Stroke.

Intravenous thrombolysis (IVT) with tenecteplase has been associated with better clinical outcomes in acute ischemic stroke (AIS) patients with confirmed large vessel occlusions compared to IVT with alteplase. However, the utility of tenecteplase for the treatment of all AIS patients eligible for IVT has not been established. We compared the safety and efficacy of tenecteplase versus alteplase in AIS patients by analyzing propensity score matched data from 20 centers participating in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients receiving IVT with tenecteplase were matched with up to 3 patients receiving alteplase from the same center. The primary outcome of interest was the distribution of 3-month functional outcomes. Secondary outcomes included the rates of patients with symptomatic intracranial hemorrhage (SICH) in the first 24hours, excellent (modified Rankin Scale [mRS] score=0-1) or good (mRS score=0-2) functional outcome, and all-cause mortality at 3 months. A total of 331 tenecteplase-treated AIS patients were matched to 797 patients treated with alteplase (median age=70 years, 43.9% women, median National Institutes of Health Stroke Scale score=11, interquartile range=6-17). Patients treated with tenecteplase had better 3-month functional outcomes (common odds ratio [OR]=1.54, 95% confidence interval [CI]= 1.18-2.00) with higher odds of good functional outcome (OR=2.00, 95% CI=1.45-2.77) and a lower likelihood of all-cause mortality (OR=0.43, 95% CI=0.27-0.67) at 3 months, compared to alteplase-treated patients. No difference was found in the likelihood of the 3-month excellent functional outcomes (OR=1.31, 95% CI=0.96-1.78) and 24-hour SICH (1.0% vs 1.3%, OR=0.72, 95% CI=0.20-2.64). IVT with tenecteplase was associated with better 3-month clinical outcomes compared to IVT with alteplase in AIS patients, with no increased risk of symptomatic intracranial bleeding. ANN NEUROL 2022;92:349-357.

Direct to angiosuite strategy versus standard workflow triage for endovascular therapy: systematic review and meta-analysis

BackgroundReducing stroke workflow times when performing endovascular thrombectomy is associated with improvement in clinical outcomes. We compared outcomes among large vessel occlusion (LVO) stroke patients following the direct to angiosuite...

Abstract WP123: Comparison Of Surgical Versus Medical Therapy In Malignant Posterior Circulation Infarction: A Systematic Review And Meta-analysis

Introduction: Whilst surgical decompression in malignant middle cerebral artery infarction is well established, its role in malignant posterior circulation infarction (MPCI) is unclear. Recent small cohort studies suggest that neurosurgery in this group may be beneficial. This systematic review and meta-analysis aims to compare outcomes of MPCI patients undergoing surgical intervention versus medical therapy. Methods: Medline, Embase and Cochrane were searched from inception until 2 April 2021. Studies were included if they evaluated patients with posterior circulation stroke treated with neurosurgical intervention. Observational cohort studies and case series with death and functional outcome data were included. Death was defined as Glasgow Outcome Scale (GOS) 1 and modified Rankin scale (mRS) 6, or extracted from the text. Favourable functional outcome was defined as mRS 0-2, GOS 4-5, Barthel Index 91-100 or extracted from text at the latest follow-up period. 6673 studies were filtered, with 31 studies included for data extraction, of which 8 studies included both a surgical and medical therapy group. Random effects meta-analysis, analysis of proportions and meta-regression were performed. Results: The medical therapy cohort (n=235) had significantly better odds of good functional outcome (GFO) than the surgical cohort. There was no significant difference in odds of death between the two groups (Figure 1). Amongst surgical patients (n=184), 18% died and 55% had GFO. On meta-regression, the proportion of patients with atrial fibrillation and hydrocephalus was negatively associated with odds of death and GFO respectively (both p<0.05). Conclusion: In patients with MPCI, neurosurgery did not improve functional outcome or mortality in comparison with medical therapy. Larger cohort studies are warranted to resolve this clinical equipoise.

Abstract WMP41: Heart Failure, Age And Functional Outcomes After Ischemic Stroke

Background: The presence of cardiovascular risk factors and associated diseases, including heart failure (HF), has been associated with worse outcomes following stroke. It is unclear however whether the association between HF and poor outcomes persists in younger cohorts, in whom HF is less often a consequence of long-standing cardiovascular disease. We hypothesize prevalent heart failure has differential associations with post-stroke functional outcomes across age groups. Methods: We performed a retrospective analysis of patients admitted with acute ischemic stroke at Columbia University Medical Center between 1990-2020 for whom adjudicated data was available at the time of analyses. Demographic, clinical variables including NIHSS and TPA administration, and functional outcomes were extracted. Good functional outcome was defined as a discharge modified Rankin score ≤ 2. Multivariable regression models were used to determine adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Results: Of the 855 patients hospitalized with ischemic stroke, 47% were women, 32% were ≤ 60 years, and 139 (16%) had pre-existing heart failure. Good functional outcome was seen in 456 (53%), in patients who had a mean age of 67.2 (16.4) years. Age as a continuous measure modified the effect of prevalent heart failure on the odds of good functional outcome (P = 0.001 for interaction). Among patients ≤ 60 years, after controlling for cardiovascular risk factors, NIHSS and TPA use, prevalent heart failure was associated with greater odds of good functional outcome (aOR: 1.33, 95% CI: 1.08-13.14) compared to young adults without HF. Among older stroke patients, HF was non-significantly associated with lower odds of good functional outcome (aOR: 0.86, 95% CI: 0.50-1.50). Conclusion: Premature heart failure (often due to congenital defects, hereditary cardiomyopathies, infections or other non-vascular etiologies) in younger stroke patients may be a marker of lower cardiovascular disease burden compared to young adults with stroke secondary to traditional stroke risk factors. These factors may play a larger role in post-stroke outcomes and recovery.

Abstract TMP50: Increased Systolic Blood Pressure In The Subacute, But Not Acute, Period After Ischemic Stroke Is Associated With Good Functional Outcome At 90 Days

Background: Prior research has shown that increased blood pressure variability (BPV) after ischemic stroke is associated with lower odds of good functional outcome, but the number, intervals between, and epochs of blood pressure measurements have not been standardized. Methods: We include patients enrolled in the FAST-MAG trial with a final diagnosis of ischemic stroke, premorbid modified Rankin Scale (mRS) of 0, 4 “early” blood pressure measurements (prehospital and 3 in the hour after arrival), and 9 “later” measurements (q4 hours from hours 4-24 and q8 hours from hours 24-48). The primary outcome was 90-day mRS of 0-1 (good outcome). The BPV exposure was the top tertile (highest level) of systolic standard deviation (SD). We fit logistic regression models adjusted for patient age, race, sex, baseline NIH Stroke Scale, tPA, endovascular therapy, mean systolic blood pressure, smoking, atrial fibrillation, hypertension, and diabetes. Results: We included 455 patients, with a mean age of 70.8 years, 46.8% female, 50.8% had tPA, 6.4% had endovascular therapy, the median baseline NIH Stroke Scale was 12 (5-19) and good outcome occurred in 152/455 (33.4%). The mean early SD was not significantly lower in patients with good outcome (p=0.12), but later SD was lower in patients with good outcome (13.5±5.6 vs. 15.1±5.6, p<0.01). The adjusted odds ratio for good outcome in the top tertile of early BPV was 1.09 (95% CI 0.63-1.89), while for the top tertile of later BPV it was 0.54 (95% CI 0.30-0.95). The predicted probability of good outcome for a range of later BPV values is seen in Figure 1. Conclusion: Increased BPV in the hours after ischemic stroke onset was not associated with 90-day good outcome, but increased BPV during hours 4-48 after hospital arrival had a significant association with lower odds of good outcome. While these results are hypothesis-generating, the rigor of outcome adjudication and standardization of blood pressure measurements strengthens the findings.

Mechanical thrombectomy versus medical care alone in large ischemic core: An up-to-date meta-analysis.

We compared outcomes and adverse events of thrombectomy versus medical management in acute ischemic stroke (AIS) patients with baseline large infarct core. We searched Ovid MEDLINE(R) ALL, Cochrane Library Clinical Controlled Trials and EMBASE from inception to January 2021 for studies comparing thrombectomy and medical management alone in AIS patients who had ASPECTS <=7 or ischemic core volume >=50 ml. Imaging modalities to valuate ASPECTS and core volume were without restriction. The functional outcome was measured by mRS (modified Rankin Scale) score 0-2 at 90 days or discharge. The safety end point included the rates of mortality and sICH (symptomatic intracranial hemorrhage) or PH2 (parenchymal hematoma type 2). Fourteen studies with a total of 2547 patients (thrombectomy n = [1197]; medical care alone [n = 1350]) fulfilled our criteria. As for patients with low ASPECTS, pooled results indicated a higher odds of good functional outcome (OR = 3.47; 95% CI 1.99 to 6.07; P < 0.0001, I2=66%) and a lower risk of mortality (OR = 0.62; 95% CI 0.46 to 0.83; P = 0.001, I2=32%) in thrombectomy group compared with no thrombectomy group, but the risk of sICH or PH2 did not differ between two groups. As for patients with large core volume, both functional outcome and safety end point between two groups showed no statistically significant difference. Thrombectomy remained safe and effective by careful selection in patients with low ASPECTS. More studies were warranted to explore contraindications for mechanical thrombectomy in AIS patients, especially in patients with large core volume.

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial

BackgroundThe optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.MethodsESCAPE-NA1 was...

CTP-guided reperfusion therapy in acute ischemic stroke: a meta-analysis.

Computed tomography perfusion (CTP) imaging could be useful in guiding reperfusion therapy or patient selection in acute ischemic stroke (AIS) patients. The aim of the current study was to determine the efficacy of the CTP-guided reperfusion therapy in AIS by performing a systematic review and meta-analysis. Medline/PubMed, Embase, and the Cochrane library were searched using the terms: "CT perfusion", "acute stroke" and "reperfusion therapy". The following studies were included: (a) studies reporting original data; (b) patients aged 18years or above; (c) patients diagnosed with anterior circulation AIS; and (d) studies with good methodological design. Twenty-two studies were finally included in the metanalysis with a total of 5, 687 patients. CTP-guided reperfusion therapy was associated with increased odds of good functional outcome without significant difference in safety profile. CTP-guided reperfusion therapy improved functional outcomes in AIS, with increased benefits to patients treated with endovascular thrombectomy.

Acute and Long-Term Outcomes of Lateralized Rhythmic Delta Activity (LRDA) Versus Lateralized Periodic Discharges (LPDs) in Critically Ill Patients.

To assess the acute and long-term outcomes for patients with lateralized rhythmic delta activity (LRDA) compared to patients with lateralized periodic discharges (LPDs). A single-center retrospective study examining consecutive patients older than 10years who had LRDA, LPDs, or both on continuous electroencephalographic (cEEG) between 12/01/2015 and 12/31/2017. Outcomes included inpatient mortality, functional outcome at follow-up, inpatient electrographic seizures, and the presence of new epilepsy at follow-up. Patients were classified into 4 groups: LRDA-only (without LPDs), LPDs-only (without LRDA), LRDA/LPDs, and control (without LRDA or LPDs). Twenty-nine patients (2.7%) were in the LRDA-only group, 76 (7%) patients were in the LPDs-only group, and 25 (2.3%) patients had both patterns (LRDA/LPDs group). 68 patients were identified as a control group. Only one patient (3%) in the LRDA-only group died during their hospitalization, compared to 21 patients (28%) in the LPDs-only group, 2 (8%) LRDA/LPDs group and 7 (10%) in the control group (p 0.003). Patients in the LPDs-only group had three times higher odds of adjusted mortality compared to the control group (p 0.05), while there was no difference in the mortality odds between the LRDA-only and control groups. Patients with LRDA-only had higher odds of good functional outcome at clinic follow-up (p 0.04). When compared to control, patients with both IIC patterns (LRDA/LPDs group) had 24.3 higher odds of acute electrographic seizures (p < 0.001), followed by patients in LPDs-only (OR 12.6, p < 0.001) and then LRDA-only (OR 9.4, p = 0.002). The odds of developing epilepsy following discharge were not increased in patients with either LRDA or LPDs (p = 0.9). Patients with LRDA had superior functional outcome compared to a higher mortality for patients with LPDs. Patients with both patterns had the highest odds of acute seizures, followed by those with only LPDs and then patients with only LRDA. There was no difference in the odds of developing new epilepsy compared to control with any IIC pattern. We hypothesize different underlying mechanisms of injury leading to the observed electrographic patterns.

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P=0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P=0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes.

Abstract TP240: Determinants of Functional Outcomes in Patients Treated With Intravenous Tissue Plasminogen Activator in Telestroke

Background: Intravenous thrombolysis in acute ischemic stroke patients (AIS) via telestroke (TS) is safe and effective, with comparable functional outcomes to patients treated at academic stroke centers. However, the association between demographic, clinical and TS logistic factors and functional outcome at 3 months in TS patients has not been studied. Identification of TS specific predictors of good outcome may guide future strategies of care delivery. Aim: To determine demographic, clinical, and TS logistic variables associated with 90-day functional outcome in AIS patients treated with IV tPA via TS. Methods: We retrospectively analyzed all TS consults treated with IV tPA between January 2016-July 2017 in our state-wide telestroke network. Patients who underwent endovascular intervention were excluded. Fisher exact and χ 2 test for categorical and Student t test for continuous variables with a significance level of &lt;0.05 were used. Stepwise logistic regression model was used to identify predictors for favorable outcome (mRS 0-2) at 3 months Results: tPA was given to 400 AIS patients via TS. Functional outcome at 90 days was obtained in 94.3% patients. Mean age was 66.8 years and 62% patients were Caucasian. Median NIHSS on presentation was 7. Medical history included hypertension (72%), diabetes (36%), hyperlipidemia (25%), atrial fibrillation (AF) (11%), and CHF (5%). Mean “onset to needle” time was 138.4 minutes(min) and mean “door to needle time” was 61.4 min. Mean “door to login” time was 26.2 min, and mean “login to tPA” time was 19.7 min. Symptomatic ICH and asymptomatic ICH occurred in 15 (5.98%) and 28(11.3%) respectively. Younger age, lower NIHSS at presentation, lower door to login time, and absence of AF and CHF were associated with higher odds of good functional outcome at 90 days in univariate analyses. In multivariate logistic regression, age (OR 0.75, 95% CI 0.67-0.84) and NIHSS at presentation (OR 0.85, 95% CI 0.82-0.89) remained independent predictors. Discussion: Younger patients and patients with low NIHSS at presentation are more likely to have good outcome post IV tPA treatment via TS. Larger studies powered to measure the impact of TS delivery variables on functional outcome are needed.

Abstract 115: CT Perfusion Identifies Patients with Poor Outcomes in The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) Trial

Background: In the ESCAPE trial, patients with large vessel occlusions and small infarct cores identified with CT/CT angiography were randomized to endovascular therapy or standard of care. CT Perfusion (CTP) was obtained in some cases, but was not utilized to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. Methods: All CTP data acquired in ESCAPE patients was analyzed centrally using a semi-automated perfusion threshold based approach. A penumbral pattern was defined as an infarct core&lt;70 mL, penumbral volume &gt;15 mL, and a total hypoperfused volume:core volume ratio of &gt;1.8. The primary outcome was a good functional outcome at 90 days (mRS 0-2). Results: CTP was acquired in 138 of 316 ESCAPE patients. Motion degraded CTP images from 9 patients were excluded. Penumbral patterns were present in 110/129 (85.3%) of patients. The rate of good functional outcome in penumbral pattern patients (53/108; 49.1%) was higher than that in non-penumbral patients (3/19; 15.8%, p=0.011). In penumbral patients, endovascular therapy increased the likelihood of good outcome (35/58; 60.3%) over those in the control group (18/50; 36%, OR=2.71, p=0.013). Only 4 of 19 non-penumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. Conclusion: The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Non-penumbral patients were much less likely to achieve good outcomes.

Abstract 8: The Impact of Nursing to Achieve Door to Drug Times of ≤ 45 Minutes in Acute Ischemic Stroke

The Impact of Nursing to Achieve Door-to-Drug Times of ≤ 45 Minutes in Acute Ischemic Stroke Background: Nursing care in a large urban university affiliated Level 1 Trauma and Comprehensive Stroke Center faces a series of competing priorities. The goal of door-to-drug for alteplase in acute ischemic stroke is 60 minutes. As time is brain, every 15 minutes saved increases the odds of good functional outcome. Objective: To evaluate the impact of alteplase reconstitution by nurses at the bedside in the Emergency Department (ED) on door to drug times compared with traditional pharmacy reconstitution process. Methods: A retrospective quality improvement project evaluating all stroke patients treated with alteplase at our institution from October 2016 - June 2017 was completed yielding 60 patients. Door-to-drug times using traditional pharmacy reconstitution from October 2016 to January 2017 (n=32) was compared to nursing reconstitution from February 2017 to June 2017 (n=28). The proportion of patients with door-to-drug times of ≤ 45 minutes in both groups was evaluated. T-test for independent means for time differences and Chi-square test of proportions was used to calculate the statistical significance in time reduction between both patient cohorts. Results: As compared to pharmacy reconstitution, the mean door-to-drug times for nursing was 15 minutes shorter with nursing (50.75 +/-21.2 vs. 65.9 +/-29.8 minutes) ( p=0.029 ). The proportion of patients within the 45 minute time window in the nursing cohort was more than double that with the pharmacy (60% [n=17] vs. 27.8% [n=7], p=0.02). Furthermore, there were no reported dosing errors in either group. Conclusions: In our study, nursing reconstitution at the bedside reduced door-to-drug times by 15 minutes and doubled the proportion of patients receiving alteplase within the 45 minute mark. Eliminating treatment delays for patients with acute ischemic stroke lowers in-hospital mortality and reduces long term disability. Efficient nursing reconstitution directly impacts the patient’s door to drug time which contributes to their functional outcome by providing a better chance for a disability-free life.

Anesthesia-Related Outcomes for Endovascular Stroke Revascularization: A Systematic Review and Meta-Analysis.

There is currently controversy on the ideal anesthesia strategy during mechanical thrombectomy for acute ischemic stroke. We performed a systematic review and meta-analysis of studies comparing clinical and angiographic outcomes of patients undergoing general anesthesia (GA group) and those receiving either local anesthesia or conscious sedation (non-GA group). A literature search on anesthesia and endovascular treatment of acute ischemic stroke was performed. Using random-effects meta-analysis, we evaluated the following outcomes: recanalization rate, good functional outcome at 90 days (modified Rankin Score≤2), symptomatic intracranial hemorrhage, death, vascular complications, respiratory complications, procedure time, and time to groin puncture. Twenty-two studies (3 randomized controlled trials and 19 observational studies), including 4716 patients (1819 GA and 2897 non-GA) were included. In the nonadjusted analysis, patients in the GA group had higher odds of death (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.66-2.45) and respiratory complications (OR, 1.70; 95% CI, 1.22-2.37) and lower odds of good functional outcome (OR, 0.58; 95% CI, 0.48-0.64) compared with the non-GA group. There was no difference in procedure time between the 2 primary comparison groups. When adjusting for baseline National Institutes of Health Stroke Scale, GA was still associated with lower odds of good functional outcome (OR, 0.59; 95% CI, 0.29-0.94). When considering studies performed in the stent-retriever/aspiration era, there was no significant difference in good neurological outcome rates (OR, 0.84; 95% CI, 0.67-1.06). Acute ischemic stroke patients undergoing intra-arterial therapy may have worse outcomes when treated with GA as compared with conscious sedation/local anesthesia. However, major limitations of current evidence (ie, retrospective studies and selection bias) indicate a need for adequately powered, multicenter randomized controlled trials to answer this question.

Review article: Why is there still a debate regarding the safety and efficacy of intravenous thrombolysis in the management of presumed acute ischaemic stroke? A systematic review and meta-analysis.

The objective of the present study is to independently and systematically assess the harms and benefits of intravenous thrombolysis for patients with presumed acute schaemic stroke. We performed a systematic review and meta-analysis of randomised clinical trials of intravenous thrombolysis compared with control in patients with presumed acute ischaemic stroke. The effectiveness of thrombolysis on functional outcome, symptomatic intracranial haemorrhage, early mortality and mortality at final follow up was assessed using a fixed-effect meta-analysis. A total of 26 studies that randomised 10 431 participants were included. The use of thrombolysis was associated with an increased odds of good functional outcome, estimated odds ratio (OR) 1.14 (95% confidence interval [CI] 1.04-1.25, P=0.004), and also a significantly increased risk of symptomatic intracranial haemorrhage, estimated OR 4.28 (95% CI 3.34-5.48, P<0.0005) and an increased risk of early mortality, estimated OR 1.51 (95% CI 1.27-1.78, P<0.0005). There was no statistically significant evidence that the effect of recombinant tissue plasminogen activator (rt-PA) was different from that of other thrombolytic agents. There was also an increase in mortality at final follow up associated with treatment with thrombolysis, estimated OR 1.17 (95% CI 1.06-1.30, P=0.003), although this result was not consistent when limited to studies of rt-PA, estimated OR 1.04 (95% CI 0.92-1.18, P=0.49). There is clear evidence of increased early mortality, increased rates of symptomatic intracranial haemorrhage and also of improved functional outcomes for patients with presumed acute ischaemic stroke treated with thrombolysis. The available data are unlikely to resolve the controversy regarding the use of intravenous thrombolysis in this population, and further randomised controlled trials are urgently required.

Intravenous Tissue Plasminogen Activator for Wake-Up Stroke: A Propensity Score-Matched Analysis

To evaluate the safety and efficacy of intravenous (IV) tissue plasminogen activator (tPA) in the treatment of wake-up stroke (WUS) using propensity score (PS) analysis. Consecutive acute ischemic stroke patients meeting inclusion criteria were retrospectively identified from our stroke registry between July 2008 and May 2014, and classified as stroke onset less than or equal to 4.5 hours treated with tPA (control; n = 369), tPA-treated WUS (n = 46), or nontreated WUS (n = 154). The primary outcome of interest for safety was symptomatic intracerebral hemorrhage (sICH), defined as parenchymal hemorrhage associated with a greater than or equal to 4-point increase in National Institutes of Health Stroke Scale (NIHSS) score. Multivariate logistic regression with adjustment for confounders and PS for receiving IV tPA assessed outcomes, along with PS-matched average treatment effect on the treated (ATT). No significant difference was found in rates of sICH between tPA-treated WUS, nontreated WUS, and controls (2.2%, .7%, and 3%, respectively), or in the odds of sICH between tPA-treated WUS and controls (OR = .53, 95% CI = .06-4.60, P = .568). Among WUS patients, tPA treatment was significantly associated with higher odds of good functional outcome in fully adjusted analyses (OR = 7.22, 95% CI = 2.28-22.88, P = .001). The ATT of tPA for WUS patients demonstrated a significantly greater decrease in NIHSS score at discharge when compared to nontreated WUS patients (-4.32 versus -.34, P = .032). Comparable rates of sICH between treated WUS and stroke onset less than or equal to 4.5 hours treated with tPA suggest that tPA may be safely used to treat WUS. Superior outcomes for tPA-treated versus nontreated WUS subjects may suggest clinical efficacy of the treatment.

Abstract 57: Main Results of the CTP to Predict Response to Recanalization in Ischemic Stroke Project (CRISP)

Background: Recent acute stroke trials showed benefit from intra-arterial thrombectomy (IAT) up to 6 hrs. We aimed to assess CT Perfusion (CTP) for selection of patients for endovascular therapy up to 18 hrs. Hypothesis: CTP target mismatch profile (TMM) identifies patients likely to benefit from IAT. Methods: The CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is an NIH funded multicenter cohort study of consecutive acute stroke patients scheduled to undergo IAT within 90 min after a baseline CTP. Volumes for the CTP ischemic core (rCBF&lt;30%) and critically hypoperfused tissue (Tmax&gt;6s) were computed with automated software (RAPID). Target Mismatch (TMM) was defined as a CBF core &lt;70 mL, a Tmax&gt;6s – core difference &gt;15mL, a Tmax&gt;6s : core ratio &gt;1.8, and a Tmax&gt;10s lesion &lt;100 mL. Reperfusion was defined as &gt;50% reduction in Tmax&gt;6s lesion volume between baseline CTP and follow-up MRI (obtained &lt;36 hrs after CTP), or TICI 2b/3 at completion of IAT if follow-up MRI was not performed/technically inadequate. Good functional outcome (GFO) was defined as mRS 0-2 on day 90. Results: Of the 201 patients enrolled, 6 had inadequate baseline CTP (3%), 3 did not undergo angiography, and 2 were lost to follow-up. Therefore, 190 patients were included; mean age 66 yrs, median NIHSS 16, median time from symptom onset to IAT 5.2 hrs (&gt;6 hrs in 40%). Rate of reperfusion was 89% (87% TICI 2b/3) and 55% had GFO. In patients with TMM (n=131), reperfusion was associated with higher odds of GFO (66% vs 29%; OR=4.3; 95% CI 1.4-13). This association remained significant when adjusted for age and NIHSS (OR=8.4; 95% CI 2.5-28). In patients without TMM (n=51), the effect of reperfusion could not be assessed, since almost all patients (95%) reperfused. Independent of reperfusion status, patients with TMM had a higher rate of GFO (61%) than those without TMM (42%, p=0.02). Conclusion: In this multicenter study, a technically adequate baseline CTP was obtained in nearly all patients and almost half underwent IAT beyond 6 hrs. Patients with the TMM profile had a high rate of GFO (61%) and a robust association between reperfusion and good outcome. These results support the feasibility of a randomized trial of IAT in an extended window using the CTP-TMM profile for patient selection.

Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue.

To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI. Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes. Among 78 patients with the target mismatch profile (mean age 66 ± 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time × reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2). The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.