Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Effect of Individualized Versus Standardized Blood Pressure Management During Endovascular Stroke Treatment on Clinical Outcome: A Randomized Clinical Trial.

BACKGROUND: Optimal blood pressure (BP) management during endovascular stroke treatment is not well established. We studied whether an individualized approach for managing BP during endovascular stroke treatment gives a better clinical outcome than an approach with standardized systolic BP targets. METHODS: The INDIVIDUATE study (Individualized Blood Pressure Management During Endovascular Treatment of Acute Ischemic Stroke Under Procedural Sedation) is a randomized clinical trial with a prospective randomized open blinded end point (PROBE) design. Patients were recruited between October 1, 2020 and July 7, 2022 at a single center at a tertiary care university hospital. Patients were eligible, when they were suffering from acute ischemic stroke of the anterior circulation with occlusions of the internal carotid artery and middle cerebral artery and a National Institutes of Health Stroke Scale score of ≥8 receiving endovascular stroke treatment in procedural sedation. The intervention consists of an individualized BP management strategy, where preinterventional baseline systolic BP (SBP) values are used as intraprocedural BP targets. As a control, the standard treatment aims to maintain the intraprocedural SBP between 140 and 180 mm Hg. The main prespecified outcome is the proportion of favorable functional outcomes 90 days after stroke, defined as a modified Rankin Scale score of 0 to 2. RESULTS: Two hundred fifty patients were enrolled and included in the analysis, mean (SD) age was 77 (12) years, 142 (57%) patients were women, and mean (SD) National Institutes of Health Stroke Scale score on admission was 17 (5.2). In all, 123 (49%) patients were treated with individualized and 127 (51%) with standard BP management. Mean (SD) intraprocedural SBP was similar in the individualized versus standard BP management group (157 [19] versus 154 [18] mm Hg; P=0.16). The rate of favorable functional outcome after 3 months was not significantly different between the individualized versus the standard BP management group (25% versus 24%; adjusted odds ratio, 0.81 [95% CI, 0.41-1.61]; P=0.56). CONCLUSIONS: Among patients treated with endovascular stroke treatment due to an acute ischemic stroke of the anterior circulation, no significant difference was seen between the individualized BP management strategy, where intraprocedural SBP was targeted to baseline values, and the standardized regimen of targeting SBP between 140 and 180 mm Hg. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04578288.

Alteplase for Stroke With Unknown Onset Time in Chronic Kidney Disease: A Pooled Analysis of Individual Participant Data.

BACKGROUND: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. METHODS: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of <60 ml/min/1.73m2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. RESULTS: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect (Pinteraction=0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55-2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls (P=0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls (P=0.539). CONCLUSIONS: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Reperfusion Without Functional Independence in Late Presentation of Stroke With Large Vessel Occlusion.

BACKGROUND: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients. METHODS: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3). RESULTS: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH. CONCLUSIONS: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04096248.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Endovascular therapy versus no endovascular therapy in patients receiving best medical management for acute isolated occlusion of the posterior cerebral artery: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Endovascular therapy (EVT) is increasingly reported for treatment of isolated posterior cerebral artery (PCA) occlusions although its clinical benefit remains uncertain. This study-level meta-analysis investigated the functional outcomes and safety of EVT and best medical management (BMM) compared to BMM alone for treatment of PCA occlusion stroke. METHODS: We conducted a literature search in PubMed, Web of Science and Embase for studies in patients with isolated PCA occlusion stroke treated with EVT + BMM or BMM including intravenous thrombolysis. There were no randomized trials and all studies were retrospective. The primary outcome was modified Rankin Scale score of 0-2 at 3 months, while safety outcomes included mortality rate and incidence of symptomatic intracranial hemorrhage (sICH). RESULTS: Twelve studies with a total of 679 patients were included in the meta-analysis: 338 patients with EVT + BMM and 341 patients receiving BMM alone. Good functional outcome at 3 months was achieved in 58.0% (95% confidence interval [CI] 43.83-70.95) of patients receiving EVT + BMM and 48.1% (95% CI 40.35-55.92) of patients who received BMM alone, with respective mortality rates of 12.6% (95% CI 7.30-20.93) and 12.3% (95% CI 8.64-17.33). sICH occurred in 4.2% (95% CI 2.47-7.03) of patients treated with EVT + BMM and 3.2% (95% CI 1.75-5.92) of patients treated with BMM alone. Comparative analyses were performed on studies that included both treatments and these demonstrated no significant differences. CONCLUSIONS: Our results demonstrate that EVT represents a safe treatment for patients with isolated PCA occlusion stroke. There were no differences in clinical or safety outcomes between treatments, supporting randomization of future patients into distal vessel occlusion trials.

Clinical Outcome After Endovascular Thrombectomy in 3 Triage Concepts: A Prospective, Observational Study (NEUROSQUAD).

BACKGROUND AND PURPOSE: NEUROSQUAD (Stroke Treatment: Quality and Efficacy in Different Referral Systems) is a prospective, observational, bicenter study comparing 3 triage pathways in endovascular stroke treatment: mothership, drip and ship (DS), and transferring a neurointerventionalist to a remote hospital for thrombectomy (drive the doctor [DD]). METHODS: Patients with anterior circulation stroke and premorbid modified Rankin Scale (mRS) score 0-3 who underwent thrombectomy within 24 hours after stroke onset were included. Primary outcome measure was good clinical outcome defined as 90-day mRS score 0-2 or clinical recovery to the status before stroke onset (ie, equal premorbid mRS and 90-day mRS). Secondary outcome measures were successful reperfusion, National Institutes of Health Stroke Scale at discharge, and mRS shift. RESULTS: In total, 360 patients were included in this study, of whom 111 patients (30.8%) were in the mothership group, 204 patients (56.7%) were in the DS group, and 45 patients (12.5%) were in the DD group. Good clinical outcome was achieved similarly in all three groups (mothership, 45.9%; DS, 43.1%; DD, 40.0%; P=0.778). Likewise, frequency of successful reperfusion was similar in all three groups (mothership, 86.5%; DS, 85.3%; DD, 82.2%; P=0.714). There was no significant difference among the groups regarding the National Institutes of Health Stroke Scale at discharge (P=0.115) and mRS shift (P=0.342). In the multivariate analysis, triage concept was not an independent predictor of good outcome (unadjusted odds ratio, 0.89 [CI, 0.64-1.23]; P=0.479). CONCLUSIONS: Our data suggest that clinical outcome after thrombectomy is similar in mothership, DS, and DD. Hence, DD can be a valuable triage option in acute stroke treatment.

Predictors for Failure of Early Neurological Improvement After Successful Thrombectomy in the Anterior Circulation.

BACKGROUND AND PURPOSE: Failure of early neurological improvement (fENI) despite successful mechanical thrombectomy in the anterior circulation is a clinically frequent occurrence. Purpose of this analysis was to define independent clinical, radiological, laboratory, or procedural predictors for fENI. METHODS: Retrospective single-center analysis of patients treated for acute ischemic stroke in the anterior circulation ensuing successful mechanical thrombectomy between January 2014 and April 2019. Patients were compared according to fENI (equal or higher National Institutes of Health Stroke Scale) and ENI (lower National Institutes of Health Stroke Scale at discharge). Thirty-eight variables were examined in multivariable analysis for association with fENI. RESULTS: Five hundred forty-nine out of 1146 patients experienced successful recanalization (modified Treatment in Cerebral Ischemia 2c-3). fENI occurred in 115/549 (20.9%) patients. Independent predictors of fENI were premorbid modified Rankin Scale (odds ratio [OR] per point [IC], 1.21 [1.00-1.46], P=0.049), end-stage renal failure (OR [IC], 12.18 [2.01-73.63], P=0.007), admission glucose (OR [IC], 1.018 [1.004-1.013] per mg/dL, P=0.001), bridging IV lysis (OR [IC], 0.57 [0.35-0.93], P: 0.024), time from groin puncture to final recanalization (OR [IC], 1.004 [1.001-1.007] per minute, P=0.015), general anesthesia during mechanical thrombectomy (OR, 2.41 [1.43-4.08], P<0.001), symptomatic intracranial hemorrhage (OR [CI], 6.81 [1.84-25.16], P=0.004), and follow-up Alberta Stroke Program Early CT Score (OR [IC], 0.76 [0.69-0.84] per point, P<0.001). In a secondary analysis, involvement of the regions internal capsule, M4 and M5 (motor cortex) were further independent predictors for fENI. Patients with ENI were more likely to experience a good outcome (modified Rankin Scale on day 90, 0-2: n=229/435 [52.8%] versus n=13/115 [11.3%]; P<0.001). CONCLUSIONS: The extent of infarction and the involvement of motor cortex and internal capsule as well as higher premorbid modified Rankin Scale, end-stage renal failure, high glucose level on admission, absence of bridging IV lysis, general anesthesia, and a longer therapy interval are presumably independent predictors for fENI in patients with successful mechanical thrombectomy.

Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials.

BACKGROUND AND PURPOSE: CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. METHODS: Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. RESULTS: Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. CONCLUSIONS: There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).

Maintenance of Acute Stroke Care Service During the COVID-19 Pandemic Lockdown.

[Figure: see text].

Differential effects of the SARS-CoV-2 pandemic on patients presenting to a neurological emergency room depending on their triage score in an area with low COVID-19 incidence.

BACKGROUND: We analyzed the effects of the SARS-CoV-2 pandemic on neurologic emergencies, depending on the patients' triage score in a setting with relatively few COVID-19 cases and without lack of resources. METHODS: Consecutive patients of a tertiary care center with a dedicated neurologic emergency room (nER) were analyzed. The time period of the first lockdown in Germany (calendar weeks 12-17, 2020) was retrospectively compared to the corresponding period in 2019 regarding the number of patients presenting to the nER, the number of patients with specific triage scores (Heidelberg Neurological Triage Score), the number of patients with stroke, and the quality of stroke care. RESULTS: A total of 4330 patients were included. Fewer patients presented themselves in 2020 compared to 2019 (median [interquartile range] per week: 134 [118-143] vs. 187 [182-192]; p = 0.015). The median numbers of patients per week with triage 1 (emergent) and 4 (non-urgent) were comparable (51 [43-58] vs. 59 [54-62]; p = 0.132, and 10 [4-16] vs. 16 [7-18]; p = 0.310, respectively).The median number of patients per week declined in categories 2 and 3 in 2020 (41 [37-45] vs. 57 [52-61]; p = 0.004, and 28 [23-35] vs. 61 [52-63]; p = 0.002, respectively. No change was observed in the absolute number of strokes (138 in 2019 and 141 in 2020). Quality metrics of stroke revascularization therapies (symptom-to-door time, door-to-needle time or relative number of therapies) and stroke severity remained constant. CONCLUSION: During the lockdown period in 2020, the number of patients with emergent symptoms remained constant, while fewer patients with urgent symptoms presented to the nER. This may imply behavioral changes in care-seeking behavior.

Hemodynamic Status During Endovascular Stroke Treatment: Association of Blood Pressure with Functional Outcome.

BACKGROUND: Optimal blood pressure (BP) management during endovascular stroke treatment in patients with large-vessel occlusion is not well established. We aimed to investigate associations of BP during different phases of endovascular therapy with reperfusion and functional outcome. METHODS: We performed a post hoc analysis of a single-center prospective study that evaluated a new simplified procedural sedation standard during endovascular therapy (Keep Evaluating Protocol Simplification in Managing Periinterventional Light Sedation for Endovascular Stroke Treatment). BP during endovascular therapy in patients was managed according to protocol. Data from four different phases (baseline, pre-recanalization, post recanalization, and post intervention) were obtained, and mean BP values, as well as changes in BP between different phases and reductions in systolic BP (SBP) and mean arterial pressure (MAP) from baseline to pre-recanalization, were used as exposure variables. The main outcome was a modified Rankin Scale score of 0-2 three months after admission. Secondary outcomes were successful reperfusion and change in the National Institutes of Health Stroke Scale score after 24 h. Multivariable linear and logistic regression models were used for statistical analysis. RESULTS: Functional outcomes were analyzed in 139 patients with successful reperfusion (defined as thrombolysis in cerebral infarction grade 2b-3). The mean (standard deviation) age was 76 (10.9) years, the mean (standard deviation) National Institutes of Health Stroke Scale score was 14.3 (7.5), and 70 (43.5%) patients had a left-sided vessel occlusion. Favorable functional outcome (modified Rankin Scale score 0-2) was less likely with every 10-mm Hg increase in baseline (odds ratio [OR] 0.76, P = 0.04) and pre-recanalization (OR 0.65, P = 0.011) SBP. This was also found for baseline (OR 0.76, P = 0.05) and pre-recanalization MAP (OR 0.66, P = 0.03). The maximum Youden index in a receiver operating characteristics analysis revealed an SBP of 163 mm Hg and MAP of 117 mm Hg as discriminatory thresholds during the pre-recanalization phase to predict functional outcome. CONCLUSIONS: In our protocol-based setting, intraprocedural pre-recanalization BP reductions during endovascular therapy were not associated with functional outcome. However, higher intraprocedural pre-recanalization SBP and MAP were associated with worse functional outcome. Prospective randomized controlled studies are needed to determine whether BP is a feasible treatment target for the modification of outcomes.

Direct Transfer to Angio-Suite Versus Computed Tomography-Transit in Patients Receiving Mechanical Thrombectomy: A Randomized Trial.

BACKGROUND AND PURPOSE: To quantify workflow metrics in patients receiving stroke imaging (noncontrast-enhanced computed tomography [CT] and CT-angiography) in either a computed-tomography scanner suite (CT-Transit [CTT]) or an angio-suite (direct transfer to angio-suite-[DTAS]-using flat-panel CT) before undergoing mechanical thrombectomy. METHODS: Prospective, single-center investigator initiated randomized controlled trial in a comprehensive stroke center focusing on time from imaging to groin puncture (primary end point) and time from hospital admission to final angiographic result (secondary end point) in patients receiving mechanical thrombectomy for anterior circulation large vessel occlusion after randomization to the CTT or DTAS pathway. RESULTS: The trial was stopped early after the enrollment of n=60 patients (CTT: n=34/60 [56.7 %]; DTAS: n=26/60 [43.3%]) of n=110 planned patients because of a preplanned interim analysis. Time from imaging to groin puncture was shorter in DTAS-patients (in minutes, median [interquartile range]: CTT: 26 [23-32]; DTAS: 19 [15-23]; P value: 0.001). Time from hospital admission to stroke imaging was shorter in patients randomized to DTAS (CTT: 12 (7-18); DTAS: 21 (15-25), P value: 0.007). Time from hospital admission to final angiographic reperfusion was comparable between patient groups (CTT: 78 [58-92], DTAS: 80 [66-118]; P value: 0.067). CONCLUSIONS: This trial showed a reduction in time from imaging to groin-puncture when patients are transferred directly to the angiosuite for advanced stroke-imaging compared with imaging in a CT scanner suite. This time saving was outweighed by a longer admission to imaging time and could not translate into a shorter time to final angiographic reperfusion in this trial.

Time Metrics to Endovascular Thrombectomy in 3 Triage Concepts: A Prospective, Observational Study (NEUROSQUAD).

Background and Purpose- NEUROSQUAD (Stroke Treatment: Quality and Efficacy in Different Referral Systems) is a prospective, observational, bi-center study comparing 3 triage pathways in endovascular stroke treatment: mothership (MS), drip and ship (DS) and transferring a neurointerventionalist to a remote hospital for thrombectomy (drive the doctor [DD]). Methods- Between February and October 2018, all stroke patients undergoing thrombectomy at 2 university hospitals and 2 associated remote hospitals were included. Primary outcome measures were time from onset to groin puncture and time from imaging to groin puncture. Secondary outcome measures were time from onset to imaging and time from onset to thrombolysis. Results- In total, 440 patients were included (mothership 32.3%, DS 55.9%, DD 11.8%). Median time from onset to groin puncture (168 minutes) and time from imaging to groin puncture (51 minutes) were the shortest in the mothership group. Time from onset to groin puncture (DD median 225 versus DS median 300 minutes; P=0.001) and time from imaging to groin puncture (DD median 118 versus DS median 172 minutes; P<0.001) were shorter in the DD group compared with DS. Time from onset to imaging was similar among mothership, DS, and DD (P=0.363). In patients receiving thrombolysis, time from onset to needle was similar among the groups (P=0.620). Conclusions- The NEUROSQUAD study adds evidence that DD may be a feasible alternative to DS, leading to shorter delay between symptom onset and groin puncture. Both are time-wise inferior compared with mothership, though.

Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). INTERPRETATION: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. FUNDING: None.

Intravenous thrombolysis for suspected ischemic stroke with seizure at onset.

OBJECTIVE: Seizure at onset (SaO) has been considered a relative contraindication for intravenous thrombolysis (IVT) in patients with acute ischemic stroke, although this appraisal is not evidence based. Here, we investigated the prognostic significance of SaO in patients treated with IVT for suspected ischemic stroke. METHODS: In this multicenter, IVT-registry-based study we assessed the association between SaO and symptomatic intracranial hemorrhage (sICH, European Cooperative Acute Stroke Study II definition), 3-month mortality, and 3-month functional outcome on the modified Rankin Scale (mRS) using unadjusted and adjusted logistic regression, coarsened exact matching, and inverse probability weighted analyses. RESULTS: Among 10,074 IVT-treated patients, 146 (1.5%) had SaO. SaO patients had significantly higher National Institutes of Health Stroke Scale score and glucose on admission, and more often female sex, prior stroke, and prior functional dependence than non-SaO patients. In unadjusted analysis, they had generally less favorable outcomes. After controlling for confounders in adjusted, matched, and weighted analyses, all associations between SaO and any of the outcomes disappeared, including sICH (odds ratio [OR]unadjusted = 1.53 [95% confidence interval (CI) = 0.74-3.14], ORadjusted = 0.52 [95% CI = 0.13-2.16], ORmatched = 0.68 [95% CI = 0.15-3.03], ORweighted = 0.95 [95% CI = 0.39-2.32]), mortality (ORunadjusted = 1.49 [95% CI = 1.00-2.24], ORadjusted = 0.98 [95% CI = 0.5-1.92], ORmatched = 1.13 [95% CI = 0.55-2.33], ORweighted = 1.17 [95% CI = 0.73-1.88]), and functional outcome (mRS ≥ 3/ordinal mRS: ORunadjusted = 1.33 [95% CI = 0.96-1.84]/1.35 [95% CI = 1.01-1.81], ORadjusted = 0.78 [95% CI = 0.45-1.32]/0.78 [95% CI = 0.52-1.16], ORmatched = 0.75 [95% CI = 0.43-1.32]/0.45 [95% CI = 0.10-2.06], ORweighted = 0.87 [95% CI = 0.57-1.34]/1.00 [95% CI = 0.66-1.52]). These results were consistent regardless of whether patients had an eventual diagnosis of ischemic stroke (89/146) or stroke mimic (57/146 SaO patients). INTERPRETATION: SaO was not an independent predictor of poor prognosis. Withholding IVT from patients with assumed ischemic stroke presenting with SaO seems unjustified. ANN NEUROL 2019;86:770-779.

Radiation exposure per thrombectomy attempt in modern endovascular stroke treatment in the anterior circulation.

OBJECTIVE: To quantify radiation exposure (RE) of endovascular stroke treatment (EST) in the anterior circulation per thrombectomy attempt and determine causes for interventions associated with high RE. METHODS: A retrospective single-center study of an institutional review board-approved stroke database of patients receiving EST for large vessel occlusions in the anterior circulation between January 2013 and April 2018 to evaluate reference levels (RL) per thrombectomy attempt. ESTs with RE above the RL were analyzed to determine causes for high RE. RESULTS: Overall, n = 544 patients (occlusion location, M1 and M2 segments of the middle cerebral artery 53.5% and 27.2%, carotid artery 17.6%; successful recanalization rate 85.7%) were analyzed. In the overall population, DAP (in Gy cm2, median (IQR)) was 113.7 (68.9-181.7) with a median fluoroscopy time of 31 min (IQR, 17-53) and a median of 2 (IQR, 1-4) thrombectomy attempts. RE increased significantly with every thrombectomy attempt (DAP1, 68.7 (51.2-106.8); DAP2, 106.4 (84.8-115.6); p value1vs2, < 0.001; DAP3, 130.2 (89.1-183.6); p value2vs3, 0.044; DAP4, 169.9 (128.4-224.1); p value3vs4, 0.001; and DAP5, 227.6 (146.3-294.6); p value4vs5, 0.019). Procedures exceeding the 90th percentile of the attempt-dependent radiation exposure level were associated with procedural complications (n = 17/52, 29.8%) or a difficult vascular access (n = 8/52, 14%). CONCLUSIONS: Radiation exposure in endovascular stroke treatment is depending on the number of thrombectomy attempts. Radiation exposure doubles when three attempts and triples when five attempts are necessary compared with single-maneuver interventions. Procedural complications and difficult vascular access were associated with a high radiation exposure in this collective. KEY POINTS: • Radiation exposure of endovascular stroke treatment (EST) is dependent on the number of thrombectomy attempts. • Reference levels as means for quality control in hospitals performing endovascular stroke treatment should be defined by the number of thrombectomy attempts-we suggest 107 Gy cm2, 156 Gy cm2, 184 Gy cm2, 244 Gy cm2, and 295 Gy cm2 for 1 to 5 maneuvers, respectively, for EST of the anterior circulation • Cases with high rates of radiation exposure are associated with periprocedural complications and difficult anatomical access as a probable cause for a high radiation exposure.

Radiation exposure in endovascular stroke treatment of acute basilar artery occlusions-a matched-pair analysis.

PURPOSE: To determine the radiation exposure in endovascular stroke treatment (EST) of acute basilar artery occlusions (BAO) and compare it with radiation exposure of EST for embolic middle cerebral artery occlusions (MCAO). METHODS: In this retrospective analysis of an institutional review board-approved prospective stroke database of a comprehensive stroke center, we focused on radiation exposure (as per dose area product in Gy × cm2, median (IQR)), procedure time, and fluoroscopy time (in minutes, median [IQR]) in patients receiving EST for BAO. Patients who received EST for BAO were matched case by case with patients who received EST for MCAO according to number of thrombectomy attempts, target vessel reperfusion result, and thrombectomy technique. RESULTS: Overall 180 patients (n = 90 in each group) were included in this analysis. General anesthesia was conducted more often during EST of BAO (BAO: 75 (83.3%); MCAO: 18 (31.1%), p < 0.001). Procedure time (BAO: 31 (20-43); MCAO: 27 (18-38); p value 0.226) and fluoroscopy time (BAO: 29 (20-59); MCAO: 29 (17-49), p value 0.317) were comparable. Radiation exposure was significantly higher in patients receiving EST for BAO (BAO: 123.4 (78.7-204.2); MCAO: 94.3 (65.5-163.7), p value 0.046), which represents an increase by 23.7%. CONCLUSION: Endovascular stroke treatment of basilar artery occlusions is associated with a higher radiation exposure compared with treatment of middle cerebral artery occlusions.

Distal arterial occlusions in patients with mild strokes - is endovascular therapy superior to thrombolysis alone?

BACKGROUND AND PURPOSE: Safety and efficacy of endovascular thrombectomy (EVT) in patients with mild stroke syndromes is unclear, especially in distal vessel occlusions. METHODS: We analysed in our stroke database (HeiReKa) between 2002 and April 2019 safety and efficacy of EVT compared to intravenous thrombolysis (IVT) in patients with occlusions distal to the M1 segment of the middle cerebral artery and the top of the basilar artery who presented with a National Institute of Health Stroke Scale (NIHSS) below 6. Excellent (good) outcome was defined as modified rankin scale (mRS) 0-1 (0-2) or return to baseline mRS (good) after 3 months. Safety endpoints were mortality after 3 months and intracranial hemorrhage according to the Heidelberg Bleeding Classification (HBC). RESULTS: Of 4167 patients 94 met the inclusion criteria. Sixty-four patients were allocated to the IVT group and 30 to the EVT group of which 15 also received IVT; three patients (4.6%) in the IVT group received rescue EVT. Baseline characteristics did not differ but more M2 occlusions were found in the EVT group (93.3% vs. 64.1%, p = 0.02). Intracranial bleeding occurred more often in EVT patients (HBC class 2: 13.3% vs. 1.6%, p = 0.01). Excellent and good outcome were not significantly different (75% vs. 70%, p = 0.65 and 87.5% vs. 73.3%, p = 0.14). Mortality was significantly lower in IVT patients (1.6% vs. 13.3%, p = 0.04). CONCLUSION: Rates of excellent and good outcome after IVT or EVT were almost similar, but safety parameters were increased after EVT. EVT may be considered in selected patients after careful risk/benefit analysis.