Welcome to the WSC 2022 Interactive Program

Background and Aims

There is limited high-quality data to prove the benefit of endovascular treatment (EVT) in patients ≥80 with large vessel occlusion (LVO) acute ischemic stroke. We aimed to evaluate the outcomes and safety of reperfusion therapy in patients ≥80 in a real-world setting.

Methods

A prospective study of consecutive patients aged ≥80 was performed between October 2019 and December 2020. Baseline characteristics, treatment, Thrombolysis in Cerebral Infarction scale (TICI), functional outcomes (modified Rankin Scale; mRS), and symptomatic intracranial hemorrhage were analyzed. Good functional outcome was defined as mRS ≤2 at 90-days.

Results

Of the 68 LVO strokes included, there were 30.9% (21/68) of patients received bridging therapy with alteplase, and the rate of successful recanalization (TICI ≥2b) was 88.2% (60/68). Good functional outcome (mRS ≤2) was observed in 17.6% (12 of 68) at 90-days. Symptomatic intracranial hemorrhage occurred in 11.76% (8 of 68) patients. Compared with unsuccessful reperfusion (11.8%, 8 of 68), patients with successful recanalization had a significant (P=0.002) shift of mRS distribution with lower rates of very severe disable mRS 5-6 (33.3% [20/60] versus 87.5% [7/8], P=0.005) and lower mortality at 90-days (26.7% [16/60] versus 87.5% [7/8], P=0.002). No significant difference in symptomatic intracranial hemorrhage between the two groups (11.7% (7 of 60) versus 12.5% (1 of 8), P=0.75).

Conclusions

EVT may be performed safely and effectively in patients aged ≥80 despite less frequent favorable outcomes. Decision-making should not withdraw based solely on high age.

Background and Aims

In patients with large vessel occlusion (LVO) stroke, the effect of systemic iron status has not been explored thus far to assess clinical outcomes. We investigated the predictive value of systemic iron status in evaluating clinical outcomes in acute stroke patients with LVO treated with reperfusion therapy.

Methods

We enrolled 747 patients with LVO treated with endovascular treatment (EVT) in this study. The primary outcome measure was a poor outcome at 3 months, defined as a modified Rankin Scale score of 3−6. All enrolled patients were measured serum iron, ferritin, transferrin, and total iron-binding capacity (TIBC) levels.

Results

High ferritin level was significantly associated with a poor outcome at 3 months in LVO patients treated with EVT (OR = 1.60, 95% CI [1.14−2.23], p = 0.006). The mortality rate was also significantly higher in the high ferritin group than in the low ferritin group (OR = 2.22, 95% CI [1.22−4.06], p = 0.009). Low iron or transferrin levels showed an association with a poor outcome at 3 months. However, these differences were not statistically significant (OR = 0.73, 95% CI [0.53−1.01], P = 0.065; OR = 0.86, 95% CI [0.62−1.20], p = 0.386, respectively). TIBC was not significantly associated with a poor outcome at 3 months.

Conclusions

Our findings suggest that a high ferritin level is an independent predictor of a poor outcome and mortality at 3 months after EVT in patients with LVO. Elevated serum ferritin, but not serum iron, maybe a molecular biomarker for neuroprotection after EVT.

Background and Aims

BACKGROUND: Medium vessel occlusions (MeVOs), that is, occlusion of the M2/M3 middle cerebral artery(MCA), A2/3 anterior cerebral artery(ACA) and P2/3 posterior cerebral artery(PCA) segments, account for 25–40% of all acute ischemic strokes. The efficacy and safety of endovascular thrombectomy in these occlusions has not been studied in detail.

AIMS AND OBJECTIVES: To assess the efficacy and safety of endovascular thrombectomy for acute ischemic stroke due to Medium Vessel occlusions (MeVOs) at a tertiary level center.

Methods

We retrospectively analyzed data from our institutional registry of endovascular mechanical thrombecomy for acute ischemic strokes due to medium vessel occlusions (M2,M3 MCA/ A2,A3 ACA and P2 PCA).Besides various demographic parameters,we collected final recanalization rates[using Thrombolysis in Cerebral Infarction (TICI) score].All the intra-procedural complications (haemorrhage, vasospasm) were also analysed. Clinical outcome was analysed using modified ranking score (mRS) on 7th day post procedure/discharge (whichever is earlier) and at the end of 3 months.

Results

From November 2016, out of 270 consecutive mechanical thrombectomies for acute ischemic stroke, 46 patients were treated for medium vessel occlusions (MeVOs)(Male:female=29:17,mean age 61.3years, mean NIHSS 10.5). Majority (91.3%) of the procedures were done for M2/M3 MCA occlusions. Final TICI 2b/3 recanalization was achieved in 40 patients(86.9%)(average number of passes 1.9). Intra-procedural complications were observed in 6 patients.Favourable modified ranking score(mRS 0-2) was achieved in approximately 60 % patients(27/45) at the end of 7 days and in 77.2 %(34/44) at the end of 3 months.

Conclusions

Our data for endovascular thrombectomy for patients with medium vessel occlusions(MeVOs) suggests good efficacy and functional outcomes.

Background and Aims

The effect of cholesterol on the functional outcome after endovascular thrombectomy (EVT) is still controversial. This study aimed to investigate whether the lipid profile is associated with the EVT prognosis

Methods

We retrospectively analyzed patients with emergent large vessel occlusion who underwent EVT. The blood lipid levels were measured in the fasting state, one day after admission. We divided patients into terciles of serum total cholesterol (TC) levels and compared the clinical characteristics among the groups. The factors associated with a good outcome at 3-months (modified Rankin scale 0–2) were investigated, considering the stroke mechanism and recanalization status.

Results

Among 274 patients, good outcomes were observed in 108 (39.4%) patients. Low initial severity (Odds ratio (OR), 0.90, 95% Confidence interval (CI), 0.858–0.954; p<0.001) and high TC level (1.01, 1.00–1.014; p=0.041) were associated with good outcomes. In patients with cardioembolism, young age (0.954, 0.917–0.993; p=0.021), low initial severity (0.921, 0.858–0.989; p=0.024) and high TC level (1.01, 1.01–1.024; p=0.036) were associated with good outcomes. The lipid profile was not associated with a functional outcome in those with large artery atherosclerosis. In patients with complete recanalization, young age (0.97, 0.941–0.994; p=0.016), low initial severity (0.91, 0.864–0.961; p=0.001), absence of diabetes (0.45, 0.218–0.947; p=0.035) or any hemorrhage (0.33, 0.142–0.760; p=0.009), and high TC level (1.01, 1.00 1.016; p=0.031) were associated with good outcomes.

Conclusions

A high TC level was associated with favorable outcomes after EVT, especially in patients with cardioembolism and complete recanalization.

Background and Aims

Considering the limited availability of data on Acute Ischemic Stroke (AIS) in Asian or Pacific Islander (API) patients, we aimed to determine the predictors of In-Hospital Mortality (IHM) following mechanical thrombectomy (MT) in this population, using the Artificial Neural Network (ANN) model, in a national cohort from the United States.

Methods

We identified AIS-MT related hospitalizations (n=22705) in API patients (n=720,3.2%) using 2018’s National Inpatient Sample (NIS) database. ANN’s predictive factors were selected for this cohort. AIS-MT IHM was randomly split (80%:20%) between training (n=114,79.2%) and testing data sets (n=30,20.8%). Training data was used to calibrate ANN while testing data was used to evaluate the accuracy of the algorithm. The frequency of incorrect prediction between training and testing data was compared and the area under the Receiver Operating Curve (AUC) was measured to determine ANN’s efficacy in predicting IHM following AIS-MT.

Results

The API cohort admitted for AIS-MT (n=720) consisted of older (71±14years), females (50.7%) primarily on Medicare (61.1%) with a prior history of stroke (12.5%) and a mean length of stay of 8±6 days. The all-cause-IHM was 10.4% (n=75). Training data showed a reduced error rate in the training vs testing model (8.8% vs.16.7%) signifying improved accuracy. Normalized predictors are displayed in Fig. 1A. The AUC was 0.733 (Fig. 1B) showing an acceptable ANN model for inpatient mortality in AIS-MT.

Conclusions

The ANN model successfully revealed the order of prevalent predictors for all-cause-IHM that can be utilized clinically to improve survival in high-risk patients.

Background and Aims

Platelets are involved in inflammatory thrombosis in acute ischemic stroke (AIS) and severe Covid-19 infection. Glenzocimab, a humanized antibody fragment targeting platelet glycoprotein VI, has been assessed in two different indications. In AIS, with a single IV dose of 1000 mg to improve the efficacy of reperfusion therapies, in Covid-19, with 1000 mg over 3 consecutive days for acute respiratory distress syndrome (ARDS) treatment.

Methods

ACTIMIS (NCT03803007) was a safety and efficacy, dose-finding clinical study. Patients were randomly assigned to placebo or glenzocimab in an initial escalating dosage scheme from 125 to 1000 mg, then to 1000 mg or placebo in 1:1 parallel groups. The primary endpoint was safety focusing on intracranial hemorrhages (ICHs).

GARDEN (NCT04659109) was an exploratory efficacy and safety clinical trial. Patients randomized 1:1 to glenzocimab or placebo. Safety was a key secondary endpoint.

Results

Within ACTIMIS, 166 patients were enrolled, 66 (40%) reported as ICH; 6 were symptomatic ICH: on glenzocimab 1/102 patients (1%), on placebo 5/64 (8%); 60 displayed non-symptomatic ICHs, on glenzocimab 30/102 (29%), on placebo 30/64 (47%). Twenty all-cause deaths were reported, 8/102 (8%) on glenzocimab and 12/64 (19%) on placebo. In GARDEN, safety analysis in 61 patients confirmed the favorable profile of glenzocimab with no mortality, no serious drug-related adverse event, no major bleeding. All results are consistent with those from phase I in healthy volunteers (Arterioscler Thromb Vasc Biol. 2019;39).

Conclusions

This favorable safety profile within three clinical studies allowed glenzocimab, a novel antithrombotic, to enter a larger ongoing phase II/III study, ACTISAVE (NCT05070260).

Background and Aims

Stroke caused from large vessel occlusion (LVO) has emerged as the most common stroke subtype worldwide. Intravenous recombinant tissue plasminogen activator administration (IV-rtPA) and additional intraarterial thrombectomy (IA-Tx) is regarded as standard treatment. On this study, authors try to find the early recanalization rate of IV-rtPA in LVO patient, and the significant of P/D-mismatching on treatment results.

Methods

300 patients who treated IV-rtPA with or without IV-Tx, conformed anterior circulation LVO were analyzed retrospectively. Brain CT-angiography (CTA) was an initial imaging study and acute stroke MRA was followed after the IV-rtPA. Early recanalization rate was evaluated by acute MRA image or cerebral angiography, and also authors analyzed treatment results according to the P/D-mismatching or not.

Results

Early recanalization rate of LVO after IV-tPA was 12.0% (36/300). And in the recanalized patients, favorable outcome (mRS, 0-2) was 69.4% (25/36) while it was 32.1% (42/131, P=0.000) in non-recanalized patients. Among 264 patients, non-recanalized after IV-rtPA patients and undertook additional IA-Tx, clinical outcome was better than not undertook additional IA-Tx (favorable outcome was 42.9% vs. 32.1%, p=0.046). And among the additional IA-Tx patient (133 patients), favorable outcome was high 50.0% (52/104) in P/D-mismatching patient (52/104=50.0% vs, 5/29=17.2%, p=0.001) than P/D-matching patients. In this analysis, P/D-mismatching favored in clinical outcome except significant hemorrhage complication rate (p=0.202).

Conclusions

Recanalization rate of IV-rtPA in LVO patient was 12.0% in our study and in recanalized patients shows better treatment results. The P/D-mismatching influence on the recanalization and clinical outcomes of IV-rtPA and IA-Tx.

Background and Aims

This study intends to review our center’s experience with mechanical thrombectomy and identify factors that affect clinical outcome.

Methods

We did a retrospective chart review of acute ischemic stroke patients who underwent mechanical thrombectomy (MT) at our hospital (University of Alberta Hospital, Edmonton, Canada) over three years starting January 2017 to April 2020. Clinical outcome was measured using a 90-day home-time. Patients with good premorbid functional status who presented with disabling neurological deficits within 6 hours from onset, late-window patients with favorable perfusion mismatch, and large vessel occlusion were included. Statistical analysis including Cragg hurdle regression conducted using STATA-16.

Results

Among the consecutive 255 stroke patients treated with MT, 115 (45.1%) received intravenous thrombolysis (IVT). Median age was 71 years, 48.6% were females, median NIHSS 17, 68.2% M1 occlusion, and 90-day mortality of 26.7%. 37.7% had home-time of more than 50 days (mRS equivalent 0-2) and 26.3% had home-time more than 80 days (mRS equivalent 0-1). An increase in age by 5 years reduces the home-time by 4 days, (p<0.001), an increase in the NIHSS by 4 reduces the home-time by 6 days (p<0.001), diabetes decreases the home-time by 11 days (p-0.02), and MT with IVT increases the home-time by 16 days (p<0.001). However, no significant difference in the predicted home-time by sex, hypertension, dyslipidemia, atrial fibrillation, smoking, and previous stroke.

Conclusions

Among patients who underwent MT, older age, higher NIHSS, and diabetes were negative predictors, and IVT was a positive predictor of 90-day home-time.

Background and Aims

Hypoperfusion intensity ratio (HIR) correlates with collateral status in acute ischemic stroke (AIS) patients, yet its impact on outcomes of endovascular treatment (EVT) in late time windows remains unknown. This study aims to evaluate associations between HIR and functional outcome after EVT in the 6-24-hour time window.

Methods

We conducted a prospective study of consecutive AIS patients with anterior circulation large-vessel occlusion who underwent EVT within 6 to 24 hours after last seen well between June 2020 and May 2021. Infarct volume and penumbral regions on perfusion imaging were measured by RAPID software. HIR (defined as time-to-maximum [TMax] >10/ TMax >6 seconds) was dichotomized into low (<0.4) versus high (>=0.4) subgroups as well as quartiles. Infarct growth velocity was calculated as the baseline infarct volume divided by the delay from onset to perfusion imaging. Good functional outcome was defined as modified Rankin scale <=2 at 90-days.

Results

162 patients were included; median HIR was 0.3 (IQR 0.1–0.5); 67.3% (109/162) had HIR <0.4. Infarct growth rate and volumes increased with HIR quartiles (P<0.001). The median HIR was significantly lower in patients with a good functional outcome at 90-days (0.2 vs 0.4; P<0.001). The low HIR group had lower NIHSS scores (P=0.001), slower infarct growth (P<0.001), smaller infarct volume (P=0.005), and more favorable outcome (54.1% vs 28.3%; P=0.002). Low HIR independently predicted a favorable outcome (OR=2.3 [95% CI, 1.03–5.1], P=0.043).

Conclusions

HIR correlates with infarct evolution, and may serve as predictor of functional outcomes after EVT among patients with large-vessel occlusion in late time windows.

Background and Aims

Despite successful recanalization, only 27% of the patients were disability-free at 90 days in previous mechanical thrombectomy (MT) trials. Surprisingly, even after revascularization, it is reported that around 40% showed hypofusion area on the perfusion imaging at the end of the intervention. Therefore, we aim to investigate factors related to hypoperfusion following the successful thrombectomy.

Methods

We retrospectively reviewed 145 patients treated with mechanical thrombectomy that resulted in angiographic findings of successful recanalization, defined as a TICI score of 2b or greater. All patients took arterial spin-labeling (ASL) perfusion weighted image (PWI) within 3-days after the procedure. We classified the patients into hypoperfusion after MT and control groups and we compared their clinical details. Multivariate analysis was performed to investigate independent predictors of hypoperfusion after successful MT.

Results

Of a total of 145 patients who received successful MT, 40 (27.6%) showed hypoperfusion on follow-up ASL PWI. Hypoperfusion after MT group showed more hemorrhagic transformations (55% vs. controls 35.2%, p=0.001) and unfavorable functional outcomes at 90 days (mean modified Rankin scale score 3.18 vs. controls 2.13, p=0.002). In the multivariate analysis, active cancer (Odds ratio [OR]=5.948, p=0004), uncontrolled diabetes mellitus (OR=1.68, p=0.004), and longer procedure time (OR=1.123, p=0.002) were independent predictors of hypoperfusion after successful recanalization.

Conclusions

If the active caner or uncontrolled diabetes is accompanied or the procedure time is prolonged, the cerebral blood flow was not improved even after a successful MT. Further research is needed on novel treatments that can enhance perfusion conditions in these cases.

Background and Aims

A plaque may rupture with high risk of subsequent thrombus mediated acute clinical events such as myocardial infarction and stroke. Catheter-based lasers have been extensively studied as an effective method to treat thrombosis. The aim of this study was to generate a rabbit model of carotid artery thromboembolic occlusion and the subsequent investigating the feasibility of intravascular Q-switched Nd: YAG laser inertial cavitation therapy accompanied by simultaneously intravenous PLGA- based encapsulated tPA nanoparticles administration in this model.

Methods

Briefly, New Zealand white rabbits were submitted to thromboembolic occlusion by injecting autologous blood clots through carotid artery. Then treatment group underwent intravascular Q-switched Nd: YAG laser (Frequency= 532 nm, Power= 18.5 W, Pulse Duration= 25 ns) inertial cavitation therapy accompanied by simultaneously intravenous PLGA - based encapsulated tPA nanoparticles (0.8 mg/kg) administration, wherein diagnostic B- mode ultrasound is combined with therapy system, with a goal of increased safety.

Results

Results from ultrasound imaging concurrent with catheter- based Q-switched Nd: YAG laser thrombolytic therapy, showed the collapsed capsules in the carotid artery. Also, histopathology results, showed a significant reduction in the mean value for thrombus content at the embolic region in the treatment group compared with the other groups (P<0.05).

Conclusions

Enhanced thrombolytic effect of Q-switched Nd: YAG laser, induced by collapsed capsules, accompanied by photoporation effect of laser, can cause to enhance the anti- thrombotic effect of tPA and significantly reduce the thrombus content and dilate the luminal cross-sectional area at the embolic region and lower treatment time and reduce total costs of treatment.

Background and Aims

We performed a phase 2 trial to determine whether mechanical thrombectomy (MT) alone in acute ischemic stroke patients demonstrates “promise” or a lack thereof (“futility”) compared with those treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) (historical controls).

Methods

Subjects with a baseline National Institutes of Health Stroke Scale (NIHSS) score ≥6 who presented within 4.5 hours of symptom onset with documented occlusion of intracranial internal carotid artery, or M1 or M2 segment of the middle cerebral artery on computed tomographic angiography were treated with MT alone. The primary outcome was functional independence defined by a modified Rankin scale (mRS) of 0-2 at 90 days post recruitment.

Results

The 72 subjects (median baseline NIHSS score of 17) were treated with MT with a median time from symptom onset of 180 minutes with complete and partial angiographic recanalization observed in 45 and 27 patients, respectively. Symptomatic intracerebral hemorrhage (≥4 points NIHSS score increase) within 24 hours was observed in 1 of 72 subjects. Overall, functional independence at 90 days was observed in 38 (52.8%) of 72 subjects. The rate was higher than the rate of functional independence in a comparable historical cohort of patients treated with IV rt-PA (52.8% versus 36%, p=0.033) enabling us to reject the futility hypothesis.

Conclusions

Due to the relatively high rates of functional independence at 90 days observed in this phase 2 trial, a randomized phase 3 comparing standard intravenous rt-PA followed by MT with primary MT is being planned.

Background and Aims

The cost-effectiveness of endovascular treatment (EVT) alone has not been compared with intravenous (IV) recombinant tissue plasminogen activator (r-tPA) with EVT in patients with acute ischemic stroke (AIS).

Methods

By using three sources derived from previous studies, we determined the cost of IV r-tPA, cost of staff time for administration, cost of the EVT, cost of the length of stay in the hospital, cost of supported discharge and community care costs, cost of post-hospitalization and disability. We then assessed the cost-effectiveness of EVT alone using a decision tree for the first year after AIS, and a Markov model with a 10-year horizon, including probabilistic assessment by Monte Carlo Simulations.

Results

The one-year cost was higher with IV r-tPA and EVT compared with EVT alone (incremental cost ranging between $ 3,554 and $ 13,788 per patient). The mean incremental cost-effectiveness ratio (ICER) was -$1,589, -$78,327, and -$15,471 per quality-adjusted life year gained for Cost Sources 1, 2, and 3, respectively for EVT alone compared with IV r-tPA and EVT at 10 years. The ceiling ICER (willingness to pay) for a probability of 100% that EVT alone was more cost effective ranged between $25,000 to $100,000 in the three models.

Conclusions

EVT alone appears to be cost effective, as compared with EVT and IV r-tPA, for the treatment of AIS patients presenting within 4.5 hours of symptom onset.

Background and Aims

Our aim was to investigate usefulness of the neutrophil-to-lymphocyte ratio (NLR) for predicting poor response to intravenous rtPA in whithe Caucasian ischemic stroke patients treated within 4.5 hours from the onset.

Methods

This retrospective analysis included all consecutive acute ischemic stroke patients (N=344) treated with rtPA in tertiary stroke center from 2011 to 2017. NLRs were calculated from complete blood counts obtained on admission. The patients were classified into NLR terciles (T1 <1.75, T2<2.97, T3<37.23). Neurological improvement was defined as an 8-point reduction in the NIHSS score or reaching a score of 0 to 1. Patients were followed-up to 90 days after stroke. Comparisons were made between tercile 3 and tercile 1.

Results

Patients from NLR tercile 3 were significantly older (median age 79 vs 73 years, p=0.019), had less often prestroke modified Rankin Scale (mRS) score of 0-1 (51% vs 76%, p<0.001), and longer onset-to-needle time (156 vs 110 min, p<0.001). Neurological improvement at day 7 was less frequent in patients from tercile 3 (38% vs 59% p=0.002) and mortality at day 90 was higher (27% vs 13%, p=0.020). However, the proportions of patients achieving at day 7 mRS of 0-2 or no progression from prestroke mRS was similar (48% vs 60%, p=0.085).

Conclusions

High NLR value can predict poor response to intravenous rtPA in Caucasian patients with acute ischemic stroke, especially in terms of not achieving significant neurological improvement at day 7 and death at day 90. It encourages its incorporation in already validated scores.

Background and Aims

Acute neurological deficits with seizure at onset (SAO)may reflect a transient post ictal phenomenon or due to actual stroke(AIS). Due to concerns about exposing patients with a stroke mimic to un necessary bleeding risk, SAO is considered a relative contra indication for intravenous thrombolysis( IVT)in patients with AIS . Here we investigated the prognostic significance of SAO in patients treated with IVT for suspected AIS.

Methods

We collected data on admitted patients with suspected AIS treated with IVT alone or followed by endo vascular treatment ( EVT).Out come measures were symptomatic intracranial hemorrhage (ECASS-11 criteria),all cause mortality at 3 months., 3 month functional out come on mRS .

Association between SAO and outcomes was assigned with aunadjusted logistic regression ,adjusted logistic regression ,coarsened exact matching and inverse probability weighted analysis.

Results

Out of 1900 patients treated with IVT 48 patients had SAO. In adjusted regression patients with SAO had generally less favourable out come than SAO patients .( SICH 4.2% vs 2.9% , mRS ­­≥ 3 ,48% Vs 42%, mortality 3 % Vs 2% .)After adjusting for confounding factors in adjusted,matched & weighted analyses all associations between SAO and any of the out come measures disappeared.These results were consistent regardless of whether patients had an eventual diagnosis of ischemic stroke or stroke mimic.

Conclusions

Among patients treated with IVT for suspected AIS, seizure at onset was not an independent predictor of poor prognosis. With holding IVT from other wise eligible patients with seizure at the onset of an acute stroke syndrome seems unjustified.