Endovascular Treatment for Acute Isolated Internal Carotid Artery Occlusion : A Propensity Score Matched Multicenter Study.

PURPOSE: The benefit of endovascular treatment (EVT) in patients with acute symptomatic isolated occlusion of the internal carotid artery (ICA) without involvement of the middle and anterior cerebral arteries is unclear. We aimed to compare clinical and safety outcomes of best medical treatment (BMT) versus EVT + BMT in patients with stroke due to isolated ICA occlusion. METHODS: We conducted a retrospective multicenter study involving patients with isolated ICA occlusion between January 2016 and December 2020. We stratified patients by BMT versus EVT and matched the groups using propensity score matching (PSM). We assessed the effect of treatment strategy on favorable outcome (modified Rankin scale ≤ 2) 90 days after treatment and compared reduction in NIHSS score at discharge, rates of symptomatic intracranial hemorrhage (sICH) and 3­month mortality. RESULTS: In total, we included 149 patients with isolated ICA occlusion. To address imbalances, we matched 45 patients from each group using PSM. The rate of favorable outcomes at 90 days was 56% for EVT and 38% for BMT (odds ratio, OR 1.89, 95% confidence interval, CI 0.84-4.24; p = 0.12). Patients treated with EVT showed a median reduction in NIHSS score at discharge of 6 points compared to 1 point for BMT patients (p = 0.02). Rates of symptomatic intracranial hemorrhage (7% vs. 4%; p = 0.66) and 3­month mortality (11% vs. 13%; p = 0.74) did not differ between treatment groups. Periprocedural complications of EVT with early neurological deterioration occurred in 7% of cases. CONCLUSION: Although the benefit on functional outcome did not reach statistical significance, the results for NIHSS score improvement, and safety support the use of EVT in patients with stroke due to isolated ICA occlusion.

Outcome of endovascular stroke therapy in a large mandatory stroke-registry.

BACKGROUND: Endovascular stroke treatment (EST) has become the standard treatment for patients with stroke due to large vessel occlusion, especially in earlier time windows. Only few data from population-based registries on effectiveness of EST have been published. METHODS: Baden-Wuerttemberg is the third largest state in Germany in terms of area and population and has a structured stroke concept since 1998 which includes mandatory collection of quality assurance data. In 2018 and 2019, 3820 of 39,168 ischemic stroke patients (9.8%) were treated by EST (age median 78 y, NIHSS median 14). We analyzed the clinical outcome of these patients determined with the modified Rankin Scale (mRS) at discharge from the hospital or with the initiation of palliative therapy using logistic regression analysis with adjustment for the mRS at admission, additive IVT, age, and NIHSS. RESULTS: The probability of an excellent clinical outcome (mRS 0 or 1 at discharge) and for a good clinical outcome (mRS 0-2) were significantly higher in EST-patients (odds-ratio (OR) 1.27; 95% confidence interval (95% CI) 1.13-1.43, and OR of 1.15 (95% CI 1.04-1.28). Also, the regression model showed an advantage for EST-patients with less frequent 'decision for palliative care' (OR 0.87; 95% CI 0.78-0.98). Sensitivity analysis adjusting for intracranial vessel occlusion as further factor showed similar results. CONCLUSION: Our data suggest that EST can be of benefit also for an area-wide unselected stroke population, in a large German federal state with sometimes long distance to the next thrombectomy center.

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.

MR microscopy to assess clot composition following mechanical thrombectomy predicts recanalization and clinical outcome.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for patients with a stroke and large vessel occlusion. Clot composition is not routinely assessed in clinical practice as no specific diagnostic value is attributed to it, and MT is performed in a standardized 'non-personalized' approach. Whether different clot compositions are associated with intrinsic likelihoods of recanalization success or treatment outcome is unknown. METHODS: We performed a prospective, non-randomized, single-center study and analyzed the clot composition in 60 consecutive patients with ischemic stroke undergoing MT. Clots were assessed by ex vivo multiparametric MRI at 9.4 T (MR microscopy), cone beam CT, and histopathology. Clot imaging was correlated with preinterventional CT and clinical data. RESULTS: MR microscopy showed red blood cell (RBC)-rich (21.7%), platelet-rich (white,38.3%) or mixed clots (40.0%) as distinct morphological entities, and MR microscopy had high accuracy of 95.4% to differentiate clots. Clot composition could be further stratified on preinterventional non-contrast head CT by quantification of the hyperdense artery sign. During MT, white clots required more passes to achieve final recanalization and were not amenable to contact aspiration compared with mixed and RBC-rich clots (maneuvers: 4.7 vs 3.1 and 1.2 passes, P<0.05 and P<0.001, respectively), whereas RBC-rich clots showed higher probability of first pass recanalization (76.9%) compared with white clots (17.4%). White clots were associated with poorer clinical outcome at discharge and 90 days after MT. CONCLUSION: Our study introduces MR microscopy to show that the hyperdense artery sign or MR relaxometry could guide interventional strategy. This could enable a personalized treatment approach to improve outcome of patients undergoing MT.

Deep-learning based detection of vessel occlusions on CT-angiography in patients with suspected acute ischemic stroke.

Swift diagnosis and treatment play a decisive role in the clinical outcome of patients with acute ischemic stroke (AIS), and computer-aided diagnosis (CAD) systems can accelerate the underlying diagnostic processes. Here, we developed an artificial neural network (ANN) which allows automated detection of abnormal vessel findings without any a-priori restrictions and in <2 minutes. Pseudo-prospective external validation was performed in consecutive patients with suspected AIS from 4 different hospitals during a 6-month timeframe and demonstrated high sensitivity (≥87%) and negative predictive value (≥93%). Benchmarking against two CE- and FDA-approved software solutions showed significantly higher performance for our ANN with improvements of 25-45% for sensitivity and 4-11% for NPV (p ≤ 0.003 each). We provide an imaging platform ( https://stroke.neuroAI-HD.org ) for online processing of medical imaging data with the developed ANN, including provisions for data crowdsourcing, which will allow continuous refinements and serve as a blueprint to build robust and generalizable AI algorithms.

Safety and effectiveness of IV Thrombolysis in retinal artery occlusion: A multicenter retrospective cohort study.

BACKGROUND: Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited. METHODS: From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0.3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA. RESULTS: We screened 200 patients with acute RAO and included 47 IVT and 34 non-IVT patients with complete information about recovery of vision. Visual Acuity at follow up significantly improved compared to baseline in IVT patients (∆VA 0.5 ± 0.8, p < 0.001) and non-IVT patients (∆VA 0.40 ± 1.1, p < 0.05). No significant differences in ∆VA and visual recovery rate were found between groups at follow up. Two asymptomatic ICH (4%) and one (2%) major extracranial bleeding (intraocular bleeding) occurred in the IVT group, while no bleeding events were reported in the non-IVT group. CONCLUSION: Our study provides real-life data from the largest cohort of IVT treated RAO patients published so far. While there is no evidence for superiority of IVT compared to conservative treatment, bleeding rates were low. A randomized controlled trial and standardized outcome assessments in RAO patients are justified to assess the net benefit of IVT in RAO.

IV Thrombolysis With or Without Endovascular Treatment for Suspected Ischemic Stroke in Patients With Intracranial Tumors.

BACKGROUND AND OBJECTIVES: IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce. METHODS: In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS: Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT; among them were 29 patients (28%) with additional endovascular treatment, with suspected, that is, imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in 9 and 4 patients (9% and 4%, respectively). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in 6 and 3 patients (7% and 4%), respectively. In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was 1 symptomatic nonfatal ICH (6%). Of 4 patients with tumors of the pituitary region, 2 patients (50%) had symptomatic ICH including 1 fatal ICH (25%). Tumor size was not associated with the occurrence of symptomatic ICH (odds ratio 2.8, 95% CI 0.3-24.8, p = 0.34). DISCUSSION: In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort seem to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

Access to and application of recanalizing therapies for severe acute ischemic stroke caused by large vessel occlusion.

BACKGROUND: Groundbreaking study results since 2014 have dramatically changed the therapeutic options in acute therapy for severe ischemic stroke caused by large vessel occlusion (LVO). The scientifically proven advances in stroke imaging and thrombectomy techniques have allowed to offer the optimal version or combination of best medical and interventional therapy to the selected patient, yielding favorable or even excellent clinical outcomes within time windows unheard of before. The provision of the best possible individual therapy has become a guideline-based gold standard, but remains a great challenge. With geographic, regional, cultural, economic and resource differences worldwide, optimal local solutions have to be strived for. AIM: This standard operation procedure (SOP) is aimed to give a suggestion of how to give patients access to and apply modern recanalizing therapy for acute ischemic stroke caused by LVO. METHOD: The SOP was developed based on current guidelines, the evidence from the most recent trials and the experience of authors who have been involved in the above-named development at different levels. RESULTS: This SOP is meant to be a comprehensive, yet not too detailed template to allow for freedom in local adaption. It comprises all relevant stages in providing care to the patient with severe ischemic stroke such as suspicion and alarm, prehospital acute measures, recognition and grading, transport, emergency room workup, selective cerebral imaging, differential treatment by recanalizing therapies (intravenous thrombolysis, endovascular stroke treatmet, or combined), complications, stroke unit and neurocritical care. CONCLUSIONS: The challenge of giving patients access to and applying recanalizing therapies in severe ischemic stroke may be facilitated by a systematic, SOP-based approach adapted to local settings.

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.

Location-specific ASPECTS does not improve Outcome Prediction in Large Vessel Occlusion compared to Cumulative ASPECTS.

PURPOSE: Individual regions of the Alberta Stroke Programme Early CT Score (ASPECTS) may contribute differently to the clinical symptoms in large vessel occlusion (LVO). Here, we investigated whether the predictive performance on clinical outcome can be increased by considering specific ASPECTS subregions. METHODS: A consecutive series of patients with LVO affecting the middle cerebral artery territory and subsequent endovascular treatment (EVT) between January 2015 and July 2020 was analyzed, including affected ASPECTS regions. A multivariate logistic regression was performed to assess the individual impact of ASPECTS regions on good clinical outcome (defined as modified Rankin scale after 90 days of 0-2). Machine-learning-driven logistic regression models were trained (training = 70%, testing = 30%) to predict good clinical outcome using i) cumulative ASPECTS and ii) location-specific ASPECTS, and their performance compared using deLong's test. Furthermore, additional analyses using binarized as well as linear clinical outcomes using regression and machine-learning techniques were applied to thoroughly assess the potential predictive properties of individual ASPECTS regions and their combinations. RESULTS: Of 1109 patients (77.3 years ± 11.6, 43.8% male), 419 achieved a good clinical outcome and a median NIHSS after 24 h of 12 (interquartile range, IQR 4-21). Individual ASPECTS regions showed different impact on good clinical outcome in the multivariate logistic regression, with strongest effects for insula (odds ratio, OR 0.56, 95% confidence interval, CI 0.42-0.75) and M5 (OR 0.53, 95% CI 0.29-0.97) regions. Accuracy (ACC) in predicting good clinical outcome of the test set did not differ between when considering i) cumulative ASPECTS and ii) location-specific ASPECTS (ACC = 0.619, 95% CI 0.58-0.64 vs. ACC = 0.629, 95% CI 0.60-0.65; p = 0.933). CONCLUSION: Cumulative ASPECTS assessment in LVO remains a stable and reliable predictor for clinical outcome and is not inferior to a weighted (location-specific) ASPECTS assessment.

Endovascular vs Medical Management for Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis of CLEAR and RESCUE-Japan.

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO. METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days). RESULTS: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR. DISCUSSION: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management. CLASSIFICATION OF EVIDENCE: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.

Exact Basilar Artery Occlusion Location Indicates Stroke Etiology and Recanalization Success in Patients Eligible for Endovascular Stroke Treatment.

INTRODUCTION: Endovascular stroke treatment (EST) is commonly performed for acute basilar artery occlusion (BAO). We aimed to identify the role of the exact location of BAO in patients receiving EST regarding the stroke etiology, recanalization success and prediction of favorable clinical outcome. METHODS: Retrospective analysis of 191 consecutive patients treated for BAO with EST from 01/2013 until 06/2021 in a tertiary stroke center. Groups were defined according to exact location of BAO in I: proximal third, II: middle third, III: distal third and IV: tip of the basilar artery. Univariate and multivariate analyses were performed for BAO location comparing stroke etiology, recanalization result and favorable clinical outcome according to mRS 0-3 90 days after stroke onset. RESULTS: Occlusion sides types I-IV were evenly distributed (37, 36, 60 and 58 patients). Types I and II were more often associated with large artery atherosclerosis (50 vs. 10 patients, p < 0.001). Distal/tip occlusion (types III/IV) occurred mostly in cardiac embolism or embolic stroke of unknown source (89 vs. 12 in types I/II, p < 0.001). Occlusion site correlated with the underlying stroke etiology (AUC [Area under the curve] 0.89, p < 0.0001, OR [odds ratio] for embolism in type IV: 245). Recanalization rates were higher in patients with distal occlusions (type III/IV OR 3.76, CI [95% confidence interval] 1.51-9.53, p = 0.0076). The BAO site is not predicting favorable clinical outcome. CONCLUSION: The exact basilar artery occlusion site in patients eligible for endovascular stroke treatment reflects the stroke etiology and is associated with differing recanalization success but does not predict favorable clinical outcome.

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.

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.

Comparing Poor and Favorable Outcome Prediction With Machine Learning After Mechanical Thrombectomy in Acute Ischemic Stroke.

Background and Purpose: Outcome prediction after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) is commonly performed by focusing on favorable outcome (modified Rankin Scale, mRS 0-2) after 3 months but poor outcome representing severe disability and mortality (mRS 5 and 6) might be of equal importance for clinical decision-making. Methods: We retrospectively analyzed patients with AIS and LVO undergoing MT from 2009 to 2018. Prognostic variables were grouped in baseline clinical (A), MRI-derived variables including mismatch [apparent diffusion coefficient (ADC) and time-to-maximum (Tmax) lesion volume] (B), and variables reflecting speed and extent of reperfusion (C) [modified treatment in cerebral ischemia (mTICI) score and time from onset to mTICI]. Three different scenarios were analyzed: (1) baseline clinical parameters only, (2) baseline clinical and MRI-derived parameters, and (3) all baseline clinical, imaging-derived, and reperfusion-associated parameters. For each scenario, we assessed prediction for favorable and poor outcome with seven different machine learning algorithms. Results: In 210 patients, prediction of favorable outcome was improved after including speed and extent of recanalization [highest area under the curve (AUC) 0.73] compared to using baseline clinical variables only (highest AUC 0.67). Prediction of poor outcome remained stable by using baseline clinical variables only (highest AUC 0.71) and did not improve further by additional variables. Prediction of favorable and poor outcomes was not improved by adding MR-mismatch variables. Most important baseline clinical variables for both outcomes were age, National Institutes of Health Stroke Scale, and premorbid mRS. Conclusions: Our results suggest that a prediction of poor outcome after AIS and MT could be made based on clinical baseline variables only. Speed and extent of MT did improve prediction for a favorable outcome but is not relevant for poor outcome. An MR mismatch with small ischemic core and larger penumbral tissue showed no predictive importance.

Leaving the day behind: endovascular therapy beyond 24 h in acute stroke of the anterior and posterior circulation.

Background: There is little evidence of endovascular therapy (EVT) being performed in acute ischemic stroke beyond 24 h, and that evidence is limited to anterior circulation stroke. Objective: To extend evidence of efficacy and safety of EVT after more than 24 h in both anterior and posterior circulation stroke. Methods: Local, prospectively collected registries were screened for patients with acute ischemic stroke and large-vessel occlusion who had received either EVT > 24 h after last-seen-well but <24 h after symptom recognition (EVT>24LSW) or EVT > 24 h since first (definitive) symptom recognition (EVT>24DEF). Patients treated <24 h served as a group for comparison. Favorable outcome was defined as modified Rankin scale (mRS) 0-2 or return to prestroke mRS at 3 months. Results: Between January 2014 and August 2021, N = 2347 were treated with EVT at our comprehensive stroke center, of whom n = 43 met the inclusion criteria (EVT>24LSW, n = 16, EVT>24DEF, n = 27). EVT>24LSW patients were treated at a median of 28.7 h [interquartile range (IQR) = 27.3-32.8] after last-seen-well and 7.3 h (IQR = 2.8-14.3) after symptom recognition; EVT>24DEF patients were treated 52.5 h (IQR = 26.5-94.2) after first symptoms. Favorable outcome was achieved by 23.3% (10/43) in the EVT > 24 compared with 39.4% (886/2250) in the EVT < 24 group (p = 0.04). Bleeding rates were similar across groups. Mortality was also similar [EVT > 24, 27.9% (12/43) versus EVT < 24, 25.7% (584/2264), p = 0.727; posterior circulation, EVT > 24, 41.7% (5/12) versus EVT < 24, 36.5% (92/252) p = 0.764]. Conclusion: In selected patients, EVT seems effective and safe beyond 24 h for both anterior and posterior circulation stroke.

Full Reperfusion Without Functional Independence After Mechanical Thrombectomy in the Anterior Circulation : Performance of Prediction Models Before Versus After Treatment Initiation.

BACKGROUND AND PURPOSE: Prediction of futile recanalization (FR), i.e. failure of long-term functional independence despite full reperfusion in mechanical thrombectomy (MT), is instrumental in patients undergoing endovascular therapy. METHODS: Retrospective single-center analysis of patients treated for anterior circulation LVO ensuing successful MT (mTICI 2c-3) between January 2014 and April 2019. FR was defined as modified Rankin Scale (mRS) 90 days after stroke onset > 2 or mRS > pre-stroke mRS. Multivariable analysis was performed with variables available before treatment initiation regarding their association with FR. Performance of the regression model was then compared with a model including parameters available after MT. RESULTS: Successful MT was experienced by 549/1146 patients in total. FR occurred in 262/549 (47.7%) patients. Independent predictors of FR were male sex, odds ratio (OR) with 95% confidence interval (CI) 1.98 (1.31-3.05, p 0.001), age (OR 1.05, CI 1.03-1.07, p < 0.001), NIHSS on admission (OR 1.10, CI 1.06-1.13, p < 0.001), pre-stroke mRS (OR 1.22, CI 1.03-1.46, p 0.025), neutrophile-lymphocyte ratio (OR 1.03, CI 1.00-1.06, p 0.022), baseline ASPECTS (OR 0.77, CI 0.68-0.88, p < 0.001), and absence of bridging i.v. lysis (OR 1.62, 1.09-2.42, p 0.016). The prediction model's Area Under the Curve was 0.78 (CI 0.74-0.82) and increased with parameters available after MT to 0.86 (CI 0.83-0.89) with failure of early neurological improvement being the most important predictor of FR (OR 15.0, CI 7.2-33.8). CONCLUSION: A variety of preinterventional factors may predict FR with substantial certainty, but the prediction model can still be improved by considering parameters only available after MT, in particular early neurological improvement.

Thrombolysis in stroke patients with elevated inflammatory markers.

OBJECTIVE: To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous thrombolysis (IVT). METHODS: In this prospective multicenter study from the TRISP registry, we assessed the association between WBC on admission and 3-month poor outcome (modified Rankin Scale 3-6), mortality and occurrence of symptomatic intracranial hemorrhage (sICH; ECASS-II-criteria) in IVT-treated stroke patients. WBC was used as continuous and categorical variable distinguishing leukocytosis (WBC > 10 × 109/l) and leukopenia (WBC < 4 × 109/l). We calculated unadjusted/ adjusted odds ratios with 95% confidence intervals (OR [95% CI]) with logistic regression models. In a subgroup, we analyzed the association of combined leukocytosis and elevated C-reactive protein (CRP > 10 mg/l) on outcomes. RESULTS: Of 10,813 IVT-treated patients, 2527 had leukocytosis, 112 leukopenia and 8174 normal WBC. Increasing WBC (by 1 × 109/l) predicted poor outcome (ORadjusted 1.04[1.02-1.06]) but not mortality and sICH. Leukocytosis was independently associated with poor outcome (ORadjusted 1.48[1.29-1.69]) and mortality (ORadjusted 1.60[1.35-1.89]) but not with sICH (ORadjusted 1.17[0.94-1.45]). Leukopenia did not predict any outcome. In a subgroup, combined leukocytosis and elevated CRP had the strongest association with poor outcome (ORadjusted 2.26[1.76-2.91]) and mortality (ORadjusted 2.43[1.86-3.16]) when compared to combined normal WBC and CRP. CONCLUSION: In IVT-treated patients, leukocytosis independently predicted poor functional outcome and death. Bleeding complications after IVT were not independently associated with leukocytosis.

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.