Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Cortical atrophy on baseline computed tomography imaging predicts clinical outcome in patients undergoing endovascular treatment for acute ischemic stroke.

OBJECTIVE: Multiple variables beyond the extent of recanalization can impact the clinical outcome after acute ischemic stroke due to large vessel occlusions. Here, we assessed the influence of small vessel disease and cortical atrophy on clinical outcome using native cranial computed tomography (NCCT) in a large single-center cohort. METHODS: A total of 1103 consecutive patients who underwent endovascular treatment (EVT) due to occlusion of the middle cerebral artery territory were included. NCCT data were visually assessed for established markers of age-related white matter changes (ARWMC) and brain atrophy. All images were evaluated separately by two readers to assess the inter-observer variability. Regression and machine learning models were built to determine the predictive relevance of ARWMC and atrophy in the presence of important baseline clinical and imaging metrics. RESULTS: Patients with favorable outcome presented lower values for all measured metrics of pre-existing brain deterioration (p < 0.001). Both ARWMC (p < 0.05) and cortical atrophy (p < 0.001) were independent predictors of clinical outcome at 90 days when controlled for confounders in both regression analyses and led to a minor improvement of prediction accuracy in machine learning models (p < 0.001), with atrophy among the top-5 predictors. CONCLUSION: NCCT-based cortical atrophy and ARWMC scores on NCCT were strong and independent predictors of clinical outcome after EVT. CLINICAL RELEVANCE STATEMENT: Visual assessment of cortical atrophy and age-related white matter changes on CT could improve the prediction of clinical outcome after thrombectomy in machine learning models which may be integrated into existing clinical routines and facilitate patient selection. KEY POINTS: • Cortical atrophy and age-related white matter changes were quantified using CT-based visual scores. • Atrophy and age-related white matter change scores independently predicted clinical outcome after mechanical thrombectomy and improved machine learning-based prediction models. • Both scores could easily be integrated into existing clinical routines and prediction models.

Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation.

OBJECTIVE: To investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF). METHODS: We analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke. RESULTS: Among 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy. CONCLUSIONS: Stroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed. TRIAL REGISTRATION NUMBER: ISRCTN48292829.

"But it's a nice compromise" - Qualitative multi-centre study of barriers and facilitators to acute telestroke cooperation in a regional stroke network.

BACKGROUND: Telemedical services can be used to complement on-site services when demand for specialists exceeds supply or when specialists are not evenly distributed across health systems. Using stroke as an example, this study aimed to explore how patients and staff experience telestroke cooperation in a stroke network in Germany. METHODS: We conducted a qualitative multi-method and multi-centre study combining 32 non-participant observations at one hub and four spoke hospitals with 26 semi-structured interviews with hub and spoke staff as well as stroke patients and relatives. Observation protocols and interview transcripts were analysed to identify barriers and facilitators to telestroke cooperation from the perspectives of staff, patients and relatives. RESULTS: In terms of barriers to telestroke cooperation, we found technological problems, providing the treatment for one patient from two sites, competing priorities between telestroke and in-house duties in the spoke hospitals, as well as difficulties in participating in the teleneurological examination via a videoconferencing system for older and disabled patients. In terms of facilitators, we found an overall very positive perception of telestroke provision by patients, good professional relationships within the network, and sharing of neurological expertise to be experienced as helpful for telestroke cooperation. CONCLUSIONS: We recommend better integration of telemedical services into the care pathway, fostering relationships within the network, improved technological support and resources, and more emphasis within networks, in public awareness efforts as well as in academia on the evaluation of telemedical services from the perspectives of patients and relatives, especially older patients and patients with disabilities.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Does Chronic Kidney Disease Have an Impact on the Use of Oral Anticoagulants after Stroke? An Observational Follow-Up Study.

INTRODUCTION: Chronic kidney disease is common in patients with acute ischemic stroke. We investigated whether chronic kidney disease has an impact on anticoagulation treatment recommendations after ischemic stroke or transient ischemic attack (TIA) related with atrial fibrillation (AF). MATERIALS AND METHODS: We extracted treatment-related data concerning stroke/TIA patients with AF and available estimated glomerular filtration rates (eGFR) from a monocentric prospective German stroke registry. Chronic kidney disease was defined as eGFR <60 mL/min/1.73 m2. Using uni- and multivariate logistic regression analyses, we investigated whether chronic kidney disease was associated with a lower probability to be treated with anticoagulation early after stroke. RESULTS: A total of 273 patients entered the analysis. In 242 AF patients (88.6%), oral anticoagulation was recommended after stroke. In multivariate logistic regression analysis, chronic kidney disease was not identified as an independent factor for the decision against anticoagulation (OR 1.63, 95% CI: 0.50-5.31, p = 0.421); only increasing age (OR 1.10, 95% CI: 1.00-1.21, p = 0.061) and a modified Rankin Scale >3 at discharge (OR 3.41, 95% CI: 0.88-13.24, p = 0.077) showed a nonsignificant trend for the decision to omit anticoagulation. A total of 155 of 167 patients (92.8%) were still anticoagulated at follow-up. A total of 44 patients with chronic kidney disease completed follow-up, and of those, 37 were still anticoagulated (84%). In patients without chronic kidney disease, 118/167 (70.7%) had continued anticoagulation (p = 0.310). CONCLUSION: Our results show that chronic kidney disease was not the main factor in the decision to withhold oral anticoagulation in patients with recent stroke/TIA and AF.

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. METHODS: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. RESULTS: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. CONCLUSION: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Multimodal Predictive Modeling of Endovascular Treatment Outcome for Acute Ischemic Stroke Using Machine-Learning.

BACKGROUND AND PURPOSE: This study assessed the predictive performance and relative importance of clinical, multimodal imaging, and angiographic characteristics for predicting the clinical outcome of endovascular treatment for acute ischemic stroke. METHODS: A consecutive series of 246 patients with acute ischemic stroke and large vessel occlusion in the anterior circulation who underwent endovascular treatment between April 2014 and January 2018 was analyzed. Clinical, conventional imaging (electronic Alberta Stroke Program Early CT Score, acute ischemic volume, site of vessel occlusion, and collateral score), and advanced imaging characteristics (CT-perfusion with quantification of ischemic penumbra and infarct core volumes) before treatment as well as angiographic (interval groin puncture-recanalization, modified Thrombolysis in Cerebral Infarction score) and postinterventional clinical (National Institutes of Health Stroke Scale score after 24 hours) and imaging characteristics (electronic Alberta Stroke Program Early CT Score, final infarction volume after 18-36 hours) were assessed. The modified Rankin Scale (mRS) score at 90 days (mRS-90) was used to measure patient outcome (favorable outcome: mRS-90 ≤2 versus unfavorable outcome: mRS-90 >2). Machine-learning with gradient boosting classifiers was used to assess the performance and relative importance of the extracted characteristics for predicting mRS-90. RESULTS: Baseline clinical and conventional imaging characteristics predicted mRS-90 with an area under the receiver operating characteristics curve of 0.740 (95% CI, 0.733-0.747) and an accuracy of 0.711 (95% CI, 0.705-0.717). Advanced imaging with CT-perfusion did not improved the predictive performance (area under the receiver operating characteristics curve, 0.747 [95% CI, 0.740-0.755]; accuracy, 0.720 [95% CI, 0.714-0.727]; P=0.150). Further inclusion of angiographic and postinterventional characteristics significantly improved the predictive performance (area under the receiver operating characteristics curve, 0.856 [95% CI, 0.850-0.861]; accuracy, 0.804 [95% CI, 0.799-0.810]; P<0.001). The most important parameters for predicting mRS 90 were National Institutes of Health Stroke Scale score after 24 hours (importance =100%), premorbid mRS score (importance =44%) and final infarction volume on postinterventional CT after 18 to 36 hours (importance =32%). CONCLUSIONS: Integrative assessment of clinical, multimodal imaging, and angiographic characteristics with machine-learning allowed to accurately predict the clinical outcome following endovascular treatment for acute ischemic stroke. Thereby, premorbid mRS was the most important clinical predictor for mRS-90, and the final infarction volume was the most important imaging predictor, while the extent of hemodynamic impairment on CT-perfusion before treatment had limited importance.

Impact of slice thickness on clinical utility of automated Alberta Stroke Program Early Computed Tomography Scores.

OBJECTIVES: The clinical utility of electronically derived ASPECTS (e-ASPECTS) to quantify signs of acute ischemic infarction could be demonstrated in multiple studies. Here, we aim to clinically validate the impact of CT slice thickness (ST) on the performance of e-ASPECTS software. METHODS: A consecutive series of n = 258 patients (06/2016 and 01/2019) with middle cerebral artery occlusion and subsequent treatment with mechanical thrombectomy was analyzed. The e-ASPECTS score and acute infarct volumes were calculated from baseline non-contrast CT with a software using 1-mm slice thickness (ST) (defined as ground truth) and axial reconstructions with 2-10-mm ST and correlated with baseline stroke severity (NIHSS) as well as clinical outcome (mRS) using logistic regressions. RESULTS: In comparison with the ground truth, significant differences were seen in e-ASPECTS scores with ST > 6 mm (p ≤ 0.031) and infarct volumes with ST > 4 mm (p ≤ 0.001). There was a significant correlation of lower e-ASPECTS and higher acute infarct volumes with increasing baseline NIHSS values for all ST (p ≤ 0.001, respectively), with values derived from 1 mm yielding the highest correlation for both parameters (rho, - 0.38 and 0.31, respectively). Similarly, lower e-ASPECTS and higher acute infarct volumes from all ST were significantly associated with poor outcome after 90 days (p ≤ 0.05, respectively) with values derived from 1-mm ST yielding the highest effects for both parameters (OR, 0.69 [95% CI 0.50-0.88] and 1.27 [95% CI 1.10-1.50], respectively). CONCLUSIONS: The e-ASPECTS software generates robust values for e-ASPECTS and acute infarct volumes when using ST ≤ 4 mm with ST = 1 mm yielding the best performance for predicting baseline stroke severity and clinical outcome after 90 days. KEY POINTS: • Clinical utility of automatically derived ASPECTS from computed tomography scans was shown in patients with acute ischemic stroke and treatment with mechanical thrombectomy. • Thin slices (= 1 mm) had the highest clinical utility in comparison with thicker slices (2-10 mm) by having the strongest correlation with baseline stroke severity and independent effects on clinical outcome after 90 days. • Automatically calculated acute infarct volumes possess clinical utility beyond ASPECTS and should be considered in future studies.

Safety of Mechanical Thrombectomy with Combined Intravenous Thrombolysis in Stroke Treatment 4.5 to 9 Hours from Symptom Onset.

BACKGROUND: An extended time window for intravenous thrombolysis (IVT) for acute stroke patients up to 9 hours from symptom onset has been established in recent trials, excluding patients who received mechanical thrombectomy (MT). We therefore investigated whether combined therapy with IVT and MT (IVT+MT) is safe in patients with ischemic stroke and large vessel occlusion (LVO) in an extended time window. METHODS: We retrospectively analyzed patients with anterior circulation ischemic stroke and LVO who were treated within 4.5 to 9 hours after symptom onset using MT with or without IVT. Primary endpoint was the occurrence of any intracranial hemorrhage (ICH). Multivariable logistic regression was used to adjust for potential confounders. RESULTS: In total, 168 patients were included in the study, 44 (26%) were treated with IVT+ MT. 133 (79%) patients had a M1-/distal carotid artery occlusion. Median ASPECT-Score was 8 (IQR 7-10) and complete reperfusion (mTICI 2b-3) was achieved in 132 (79%) patients. 18 (41%) of the patients in the IVT+MT group developed any ICH vs. 45 (36%) patients in the direct MT group (p=0.587). Symptomatic ICH occurred in 5 (11%) patients with IVT+MT vs. 8 (6%) patients receiving direct MT (p=0.295). In multivariable analysis, IVT+MT was not an independent predictor of ICH (adjusted for NIHSS, degree of reperfusion, symptom-onset-to-treatment time and therapy with tirofiban; OR 0.95 [95% CI 0.43-2.08], p=0.896). CONCLUSION: Mechanical thrombectomy in stroke patients seems to be safe with combined intravenous thrombolysis within 4.5 to 9 hours after onset as it did not significantly increase the risk for intracranial hemorrhage.

Dual Antiplatelet Therapy Improves Functional Outcome in Patients With Progressive Lacunar Strokes.

Background and Purpose- In 20% to 30% of patients with lacunar strokes, early neurological deterioration (END) occurs within the first days after stroke onset. However, effective treatment strategies are still missing for these patients. The purpose of this study was to analyze efficacy of dual antiplatelet therapy (DAPT) in patients presenting with END. Methods- Four hundred fifty-eight patients with lacunar strokes and corresponding neuroimaging evidence of lacunar ischemia were retrospectively screened for END, which was defined by deterioration of ≥3 total National Institutes of Health Stroke Scale points, ≥2 National Institutes of Health Stroke Scale points for limb paresis, or documented clinical deterioration within 5 days after admission. Patients with END were treated with DAPT according to in-house standards. Primary efficacy end point was fulfilled if National Institutes of Health Stroke Scale score at discharge improved at least to the score at admission. Secondary end points were Rankin Scale score, further clinical fluctuation, and symptomatic bleeding complications. Results- END occurred in 130 (28%) of 458 patients with lacunar strokes. Ninety-seven (75%) of these patients were treated with DAPT after END, mostly for 5 days. DAPT was associated with improved functional outcome. The primary end point was met in 68% (66) of patients with DAPT compared with 36% (12) of patients with standard treatment ( P=0.0019). Further clinical fluctuations were absent in 79% (77) of patients with DAPT versus 33% (11) of patients without DAPT ( P<0.001). Symptomatic bleeding complications were not observed in any patient. Conclusions- The results demonstrated potential positive effects of DAPT in patients with progressive lacunar strokes.

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage.

OBJECTIVE: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH. METHODS: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. RESULTS: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC. CONCLUSIONS: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Influence of a combined CT/C-arm system on periprocedural workflow and procedure times in mechanical thrombectomy.

OBJECTIVE: To achieve the fastest possible workflow in ischaemic stroke, we developed a CT/C-arm system, which allows imaging and endovascular treatment on the same patient table. METHODS: This prospective, monocentric trial was conducted between October 2014 and August 2016. Patients received stroke imaging and mechanical thrombectomy under general anaesthesia (GA) or conscious sedation (CS) using our combined setup comprising a CT-scanner and a mobile C-arm X-ray device. Primary endpoint was time between stroke imaging and groin puncture. We compared periprocedural workflow and procedure times with the literature and a matched patient cohort treated with a biplane angiographic system before installation of the CT/C-arm system. RESULTS: In 50 patients with acute ischaemic stroke due to large-vessel occlusion in the anterior circulation, comparable recanalization rates were achieved by using the CT/C-arm setup (TICI2b-3:CT/C-arm-GA: 85.7%; CT/C-arm-CS: 90.9%; Angiosuite: 78.6%; p = 0.269) without increasing periprocedural complications. Elimination of patient transport resulted in a significant reduction of the time between stroke imaging and groin puncture: median, min (IQR): CT/C-arm-GA: 43 (35-52); CT/C-arm-CS: 39 (28-49); Angiosuite: 64 (48-74); p < 0.0001. CONCLUSION: The combined CT/C-arm system allows comparable recanalization rates as a biplane angiographic system and accelerates the start of the endovascular stroke treatment. KEY POINTS: • The CT/C-arm setup reduces median time from stroke imaging to groin puncture. • Mechanical thrombectomy using a C-arm device is feasible without increasing peri-interventional complications. • The CT/C-arm setup might be a valuable fallback solution for emergency procedures. • The CT/C-arm setup allows immediate control CT images during and after treatment.

Influence of Renal Function on Treatment Results after Stroke Thrombectomy.

BACKGROUND: Renal dysfunction (RD) may be associated with poor outcome in ischemic stroke patients treated with mechanical thrombectomy (MT), but data concerning this important and emerging comorbidity do not exist so far. Here, we investigated the influence of RD on postprocedural intracerebral hemorrhage (ICH), clinical outcome, and mortality in a large prospectively collected cohort of acute ischemic stroke patients treated with MT. METHODS: Consecutive patients with anterior-circulation stroke treated with MT between October 2010 and January 2016 were included. RD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m2. In a prospective database, clinical characteristics were recorded and brain images were analyzed for the presence of ICH after treatment in all patients. Clinical outcome was assessed by the modified Rankin Scale (mRS) after 3 months. To evaluate associations between clinical factors and outcomes uni- and multivariate regression analyses were conducted. RESULTS: In total, 505 patients fulfilled all inclusion criteria (female: 49.7%, mean age: 71.0 years). RD at admission was present in 20.2%. RD patients were older and had cardiovascular risk factors more often. Multivariate regression analysis after adjustment for age, stroke severity, diabetes, hypertension, GFR, previous stroke, MT alone, or additional thrombolysis and recanalization results revealed that lower GFR was not independently associated with poor outcome (mRS 3-6; OR 1.13, 95% CI 0.99-1.28; p = 0.072) or ICH. However, lower GFR at admission was associated with a higher risk of mortality (OR 1.15, 95% CI 1.01-1.31; p = 0.038). Compared to admission, GFR values were higher at discharge (mean: 77.9 vs. 80.8 mL/min/1.73 m2; p = 0.046). CONCLUSIONS: We did not find evidence for an association of lower GFR with an increased risk of poor outcome and ICH, but lower GFR was a determinant of 90-day mortality after endovascular stroke treatment. Our findings encourage also performing MT in this relevant subgroup of acute ischemic stroke patients.

Adverse Events Following International Normalized Ratio Reversal in Intracerebral Hemorrhage.

BACKGROUND: Prothrombin complex concentrates (PCCs) are frequently used to reverse the effect of vitamin K antagonists (VKAs) in patients with non-traumatic intracerebral hemorrhage (ICH). However, information on the rate of thromboembolic events (TEs) and allergic events after PCC therapy in VKA-ICH patients is limited. METHODS: Consecutive VKA-ICH patients treated with PCC at our institution between December 2004 and June 2014 were included into this retrospective observational study. We recorded international normalized ratio (INR) values before and after PCC treatment, baseline clinical characteristics including the premorbid modified Rankin Scale (pmRS) score, TE and allergic event that occurred during the hospital stay. All events were classified by 3 reviewers as being 'related', 'probably related', 'possibly related', 'unlikely related' or 'not related' to treatment with PCC. To identify factors associated with TEs, log-rank analyses were applied. RESULTS: Two hundred and five patients were included. Median INR was 2.8 (interquartile range (IQR) 2.2-3.8) before and 1.3 (IQR 1.2-1.4) after PCC treatment and a median of 1,500 IU PCC (IQR 1,000-2,500) was administered. Nineteen TEs were observed (9.3%); none were classified 'related' but 9 were classified as 'possibly' or 'probably related' to PCC infusion (4.4%). One allergic reaction (0.5%), 'unlikely related' to PCC, was observed. In the whole cohort, PCC doses >2,000-3,000 IU, ICH volumes >40 ml, National Institute of Health Stroke Scale values >10 and a pmRS >2 were associated with the development of TEs (p = 0.031, p = 0.034, p = 0.050 and p = 0.036, respectively). CONCLUSIONS: Overall, INR reversal with PCC appears safe. Though no clear relationship between higher PCC dosing and TEs was observed, PCC doses between >2,000 and 3,000 IU and higher morbidity at ICH onset were associated with TEs. Hence, individual titration of PCC to avoid exposure to unnecessarily high doses using point-of-care devices should be prospectively explored.

Time-dependent parameter of perfusion imaging as independent predictor of clinical outcome in symptomatic carotid artery stenosis.

BACKGROUND: Carotid artery stenosis is a frequent cause of ischemic stroke. While any degree of stenosis can cause embolic stroke, a higher degree of stenosis can also cause hemodynamic infarction. The hemodynamic effect of a stenosis can be assessed via perfusion weighted MRI (PWI). Our aim was to investigate the ability of PWI-derived parameters such as TTP (time-to-peak) and T(max) (time to the peak of the residue curve) to predict outcome in patients with unilateral acute symptomatic internal carotid artery (sICA) stenosis. METHODS: Patients with unilateral acute sICA stenosis (≥50% according to NASCET), without intracranial stenosis or occlusion, who underwent PWI, were included. Clinical characteristics, volume of restricted diffusion, volume of prolonged TTP and T(max) were retrospectively analyzed and correlated with outcome represented by the modified Rankin Scale (mRS) score at discharge. TTP and T(max) volumes were dichotomized using a ROC curve analysis. Multivariate analysis was performed to determine which PWI-parameter was an independent predictor of outcome. RESULTS: Thirty-two patients were included. Degree of stenosis, volume of visually assessed TTP and volume of TTP ≥2 s did not distinguish patients with favorable (mRS 0-2) and unfavorable (mRS 3-6) outcome. In contrast, patients with unfavorable outcome had higher volumes of TTP ≥4 s (9.12 vs. 0.87 ml; p = 0.043), TTP ≥6 s (6.70 vs. 0.20 ml; p = 0.017), T(max) ≥4 s (25.27 vs. 0.00 ml; p = 0.043), T(max) ≥6 s (9.21 vs. 0.00 ml; p = 0.017), T(max) ≥8 s (6.86 vs. 0.00 ml; p = 0.011) and T(max) ≥10s (5.94 vs. 0.00 ml; p = 0.025) in univariate analysis. Multivariate logistic regression showed that NIHSS score on admission (Odds Ratio (OR) 0.466, confidence interval (CI) [0.224;0.971], p = 0.041), T(max) ≥8 s (OR 0.025, CI [0.001;0.898] p = 0.043) and TTP ≥6 s (OR 0.025, CI [0.001;0.898] p = 0.043) were independent predictors of clinical outcome. CONCLUSION: As they stood out in multivariate regression and are objective and reproducible parameters, PWI-derived volumes of T(max) ≥8 s and TTP ≥6 s might be superior to degree of stenosis and visually assessed TTP maps in predicting short term patient outcome. Future studies should assess if perfusion weighted imaging might guide the selection of patients for recanalization procedures.

Treatment With Prothrombin Complex Concentrate to Enable Emergency Lumbar Puncture in Patients Receiving Vitamin K Antagonists.

STUDY OBJECTIVE: Lumbar punctures are frequently necessary in neurologic emergencies, but effective oral anticoagulation with vitamin K antagonists represents a contraindication. We report the effectiveness of prothrombin complex concentrates to reverse vitamin K antagonist to enable emergency lumbar punctures, as well as evaluate lumbar puncture- and prothrombin complex concentrates-related complications. METHODS: Consecutive patients treated with prothrombin complex concentrates between December 2004 and June 2014 to enable emergency lumbar puncture were included. International normalized ratio (INR) before and after prothrombin complex concentrates treatment and the time between start of reversal treatment and lumbar puncture were recorded. A target INR of less than or equal to 1.5 was defined as effective prothrombin complex concentrates treatment. Bleeding events, thromboembolic events, and allergic reactions after prothrombin complex concentrates treatment were identified and classified as "related," "probably," "possibly," "unlikely related," or "not related" to the lumbar puncture and prothrombin complex concentrates infusion. RESULTS: Thirty-seven patients were included (64.9% men; median age 76.0 years; interquartile range [IQR] 71.0 to 84.0 years). The intervention with prothrombin complex concentrates was effective in 33 of 37 patients (89.2%; 95% confidence interval [CI], 78.4% to 97.3%). The median INR was 2.2 (IQR 1.8 to 2.9; 95% CI, 1.9 to 2.5) before and 1.3 (IQR 1.2 to 1.4; 95% CI, 1.2 to 1.3) after prothrombin complex concentrates treatment. The median time between start of prothrombin complex concentrates treatment and lumbar puncture was 135 minutes (IQR 76 to 266 minutes; 95% CI, 84 to 198 minutes). One clinically irrelevant intracranial subdural hematoma "related" to the lumbar puncture developed. No allergic reaction was observed, but 2 of 37 patients (5.4%; 95% CI, 0% to 13.5%) experienced a thromboembolic event (1 ischemic stroke, classified "unlikely related," and 1 myocardial infarction, "possibly related" to prothrombin complex concentrates treatment). CONCLUSION: Reversing the effect of vitamin K antagonist with prothrombin complex concentrates to enable emergency lumbar puncture appears effective and safe, particularly in regard to bleeding events.

Impact of sex in stroke thrombolysis: a coarsened exact matching study.

BACKGROUND: It is not established whether sex influences outcome and safety following intravenous thrombolysis (IVT) in acute stroke. As a significant imbalance exists between the baseline conditions of women and men, regression analysis alone may be subject to bias. Here we aimed to overcome this methodical shortcoming by balancing both groups using coarsened exact matching (CEM) before evaluating outcome. METHODS: From our local prospective stroke database we analyzed consecutive patients who suffered anterior circulation stroke and received IVT from 1998 to 04/2013 (n = 1391, 668 female, 723 male). Data were preprocessed by CEM, balancing for age, NIHSS, lesion side, hypertension, diabetes, atrial fibrillation, smoking, coronary heart disease, and previous stroke, which yielded a matched cohort of 502 women and 436 men (n = 938). Outcome was estimated by adjusted binomial logistic regression analysis incorporating matched weights. RESULTS: No effect of sex was seen to predict good outcome (OR 1.04, CI 0.76-1.43) or mortality (OR 1.13, CI 0.73-1.73). However, female sex was a strong independent predictor of symptomatic intracerebral hemorrhage (sICH - ECASS-II definition, OR 3.62, CI 1.77-7.41) and fatal ICH (OR 4.53, CI 1.61-12.7). CONCLUSION: In balanced groups, the two sexes showed comparable outcomes following IVT. A novel finding was the higher rate of sICH and fatal ICH in women. In this analysis we also demonstrate how CEM can reduce multivariate imbalance and thereby improve estimates, already in crude, but more importantly, in adjusted regression analysis. Further investigations of multicentre data with improved analytical approaches that yield balanced sex-groups are therefore warranted.

Repeated Intravenous Treatment with Recombinant Tissue-Type Plasminogen Activator in Patients with Acute Ischemic Stroke.

OBJECTIVE: Increased use of systemic thrombolysis, demographic changes, and higher chances of surviving first-ever strokes all lead to an increasing number of patients with recurrent stroke. However, data on repeated thrombolysis are limited. Here, we report on the safety and clinical effects of repeated intravenous recombinant tissue-type plasminogen activator (rt-PA) treatment in a large consecutive cohort of stroke patients. METHODS: We identified all stroke patients who received repeated thrombolysis. We determined safety and 3-month clinical outcome after the first and second thrombolysis. All patients received follow-up brain imaging. Good clinical outcome was defined as a modified Rankin Scale of 0-2 or recovery to the prestroke status. RESULTS: In total, 24 patients were included (i.e. 1.5% of all stroke patients treated with rt-PA at our center who survived the first treatment; male 45.8%; median age at first event: 74.5 years). No allergic or anaphylactic reactions were recorded after the first time of treatment, but oral angioedema developed once during the second treatment. No symptomatic intracerebral hemorrhage was observed. Clinical outcome was good in 75.0% after the first, but in only 41.7% after the second treatment (p = 0.021). CONCLUSIONS: Repeated thrombolysis was not associated with a higher rate of complications. However, the clinical outcome appears to be less satisfactory than after the first treatment.