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.

Clinical value of automated volumetric quantification of early ischemic tissue changes on non-contrast CT.

BACKGROUND: Quantitative and automated volumetric evaluation of early ischemic changes on non-contrast CT (NCCT) has recently been proposed as a new tool to improve prognostic performance in patients undergoing endovascular therapy (EVT) for acute ischemic stroke (AIS). We aimed to test its clinical value compared with the Alberta Stroke Program Early CT Score (ASPECTS) in a large single-institutional patient cohort. METHODS: A total of 1103 patients with AIS due to large vessel occlusion in the M1 or proximal M2 segments who underwent NCCT and EVT between January 2013 and November 2019 were retrospectively enrolled. Acute ischemic volumes (AIV) and ASPECTS were generated from the baseline NCCT through e-ASPECTS (Brainomix). Correlations were tested using Spearman's coefficient. The predictive capabilities of AIV for a favorable outcome (modified Rankin Scale score at 90 days ≤2) were tested using multivariable logistic regression as well as machine-learning models. Performance of the models was assessed using receiver operating characteristic (ROC) curves and differences were tested using DeLong's test. RESULTS: Patients with a favorable outcome had a significantly lower AIV (median 12.0 mL (IQR 5.7-21.7) vs 18.8 mL (IQR 9.4-33.9), p<0.001). AIV was highly correlated with ASPECTS (rho=0.78, p<0.001) and weakly correlated with the National Institutes of Health Stroke Scale score at baseline (rho=0.22, p<0.001), and was an independent predictor of an unfavorable clinical outcome (adjusted OR 0.97, 95% CI 0.96 to 0.98). No significant difference was found between machine-learning models using either AIV or ASPECTS or both metrics for predicting a good clinical outcome (p>0.05). CONCLUSION: AIV is an independent predictor of clinical outcome and presented a non-inferior performance compared with ASPECTS, without clear advantages for prognostic modelling.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Dynamics of cerebral perfusion and oxygenation parameters following endovascular treatment of acute ischemic stroke.

BACKGROUND: We studied the effects of endovascular treatment (EVT) and the impact of the extent of recanalization on cerebral perfusion and oxygenation parameters in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO). METHODS: Forty-seven patients with anterior LVO underwent computed tomography perfusion (CTP) before and immediately after EVT. The entire ischemic region (Tmax >6 s) was segmented before intervention, and tissue perfusion (time-to-maximum (Tmax), time-to-peak (TTP), mean transit time (MTT), cerebral blood volume (CBV), cerebral blood flow (CBF)) and oxygenation (coefficient of variation (COV), capillary transit time heterogeneity (CTH), metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF)) parameters were quantified from the segmented area at baseline and the corresponding area immediately after intervention, as well as within the ischemic core and penumbra. The impact of the extent of recanalization (modified Treatment in Cerebral Infarction (mTICI)) on CTP parameters was assessed with the Wilcoxon test and Pearson's correlation coefficients. RESULTS: The Tmax, MTT, OEF and CTH values immediately after EVT were lower in patients with complete (as compared with incomplete) recanalization, whereas CBF and COV values were higher (P<0.05) and no differences were found in other parameters. The ischemic penumbra immediately after EVT was lower in patients with complete recanalization as compared with those with incomplete recanalization (P=0.002), whereas no difference was found for the ischemic core (P=0.12). Specifically, higher mTICI scores were associated with a greater reduction of ischemic penumbra volumes (R²=-0.48 (95% CI -0.67 to -0.22), P=0.001) but not of ischemic core volumes (P=0.098). CONCLUSIONS: Our study demonstrates that the ischemic penumbra is the key target of successful EVT in patients with AIS and largely determines its efficacy on a tissue level. Furthermore, we confirm the validity of the mTICI score as a surrogate parameter of interventional success on a tissue perfusion level.

Successful implementation of best medical treatment for patients with asymptomatic carotid artery stenosis within a randomized controlled trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) can be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or best medical treatment (BMT) only. For all treatment options, optimization of vascular risk factors such as arterial hypertension, hyperlipidemia, smoking, obesity, and insufficient physical activity is essential. Data on adherence to BMT and lifestyle modification in patients with ACS are sparse. The subject of this investigation is the implementation and quality of risk factor adjustment in the context of a randomized controlled trial. METHODS: A total of 513 patients in the prematurely terminated, randomized, controlled, multicenter SPACE-2 trial (ISRCTN 78592017) were analyzed within one year after randomization into 3 groups (CEA, CAS, and BMT only) for implementation of prespecified BMT recommendations and lifestyle modifications. Measurement time points were the screening visit and visits after one month (D30), 6 months (M6), and one year (A1). Differences between groups and follow-up visits (FUVs) relative to the screening visit were investigated. FINDINGS: For all FUVs, a significant increase in statin medication (91% at A1; p < 0.0001) was demonstrated to be associated with a significant decrease (p < 0.01) in cholesterol levels (median 167 mg/dl at A1) and LDL cholesterol levels (median 93 mg/dl at A1). The lowest cholesterol levels were achieved by patients in the BMT group. Seventy-eight percent of all patients reached predefined target cholesterol levels (< 200 mg/dl), with significantly better rates in the BMT group (p = 0.036 at D30). Furthermore, a significant decrease in arterial blood pressure at all FUVs (p < 0.05) was associated with a significant increase in antihypertensive medication (96% at A1, p < 0.0001). However, only 28% of patients achieved the predefined treatment goal of a systolic blood pressure of ≤ 130 mmHg. Forty-two of a total of 100 smokers at the screening visit quit smoking within one year, resulting in a significant increase in nonsmokers at all FUVs (p < 0.0001). Recommended HbA1c levels (< 7%) were achieved in 82% without significant changes after one year. Only 7% of obese (BMI > 25) patients achieved sufficient weight reduction after one year without significant changes at all FUVs (median BMI 27 at A1; p = 0.1201). The BMT group showed significantly (p = 0.024) higher rates of adequate physical activity than the intervention groups. Furthermore, after one year, the BMT group showed a comparatively significantly better implementation of risk factor modification (77%; p = 0.027) according to the treating physician. INTERPRETATION: SPACE-2 demonstrated sustained improvement in the noninterventional management of vascular risk factors in patients treated in a clinical trial by general practitioners, internists and neurologists. The best implemented treatment targets were a reduction in cholesterol and HbA1c levels. In this context, a significant increase in statin use was demonstrated. Blood pressure control missed its target but was significantly reduced by intensification of antihypertensive medication. Patients on BMT only had better adjusted lipid parameters and were more physically active. However, all groups failed to achieve sufficient weight reduction. Due to insufficient patient recruitment, the results must be interpreted cautiously. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN78592017, Registered 16 June 2007, https://www.isrctn.com/search?q=78592017 .

Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke.

BACKGROUND: Despite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional independence after successful endovascular recanalization and test their predictive performance. METHODS: Patients with acute anterior ischemic stroke undergoing endovascular treatment between April 2015 and November 2019 were retrospectively analyzed. Only patients with premorbid modified Rankin Scale (mRS) score <3 and complete recanalization (modified Thrombolysis In Cerebral Infarction 2c/3) were included. Optimal thresholds of the most important variables predicting functional independence (mRS 0-2 after 90 days) were calculated using receiver operating characteristic curves and their predictive performance was tested in an independent dataset using machine learning algorithms. RESULTS: Overall, 371 patients met the inclusion criteria. Optimal thresholds for the overall most important variables to predict functional independence were (1) National Institutes of Health Stroke Scale (NIHSS) score ≤5 after 24 hours (area under the curve (AUC) 0.88 (95% CI 0.84 to 0.92)); (2) Alberta Stroke Program Early CT Score (ASPECTS) ≥7 on follow-up CT (AUC 0.72 (95% CI 0.68 to 0.77)); and (3) change in NIHSS score ≥8 after 24 hours (AUC 0.70 (95% CI 0.65 to 0.74)). The performance of these thresholds to predict a good outcome using machine learning in the independent dataset was evaluated for (1) NIHSS score ≤5 after 24 hours (AUC 0.76 (95% CI 0.71 to 0.81)); (2) follow-up ASPECTS ≥7 (AUC 0.64 (95% CI 0.58 to 0.70)); (3) change in NIHSS score ≥8 after 24 hours (AUC 0.61 (95% CI 0.55 to 0.67)); and (4) the combination of all three parameters (AUC 0.84 (95% CI 0.80 to 0.88)). CONCLUSIONS: After complete recanalization in acute anterior circulation ischemic stroke, a good long-term outcome could be accurately predicted reaching NIHSS score ≤5 after 24 hours.

Tandem occlusions in acute ischemic stroke - impact of antithrombotic medication and complementary heparin on clinical outcome and stent patency.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) and acute carotid stenting (ACS) of patients with acute ischemic stroke due to tandem occlusions (TO) of the anterior circulation was proven to be safe and effective, but the implications of periprocedural antithrombotic medications are only known to a limited extent. METHODS: We conducted a retrospective analysis of 162 consecutive patients who presented with TO and were treated with MT and ACS in our center. Patients initially either received dual antiplatelet therapy (DAT) or tirofiban periprocedurally. Some patients were also treated with unfractionated heparin. The frequency of intracranial hemorrhages (ICH), as well as the impact on clinical outcome and stent patency of different medical regimes, were evaluated using univariate tests and adjusted multivariate logistic regressions. RESULTS: Patients who received supportive treatment with heparin had significantly higher occurrences of any (OR, 2.46; 95% CI, 1.15 to 5.28) and symptomatic ICH (OR, 3.71; 95% CI, 1.18 to 14.95). Additionally, these patients were less likely to have a moderate clinical outcome after 90 days (modified Rankin scale 0-3; OR, 0.33; 95% CI, 0.15 to 0.72), but were more likely to have a fatal outcome after 90 days (OR, 2.84; 95% CI 1.10 to 7.31). These findings persisted in patients who received both DAT and heparin, but not for patients who received both tirofiban and heparin. CONCLUSION: Supportive administration of heparin in patients with TO and treatment with MT and ACS should be carefully considered, especially in patients who primarily receive DAT.

Electronic Alberta Stroke Program Early CT score change and functional outcome in a drip-and-ship stroke service.

BACKGROUND: Debate continues as to whether patients with acute ischemic stroke with (suspected) large vessel occlusion benefit from direct referral versus secondary transportation. AIMS: To analyze the change in early infarct signs, collaterals, and acute ischemia volume and their association with transfer time and functional outcome. METHODS: We retrospectively analyzed consecutive transfers between 2013 and 2016 for patients with anterior circulation stroke transported from referring hospitals to our center as potential candidates for thrombectomy. Alberta Stroke Programme Early CT Scores (ASPECTS) were automatically calculated on external and in-house CT using the Brainomix e-ASPECTS software, and collaterals were assessed using the e-CTA tool. Functional status after stroke using the modified Rankin scale (mRS) was obtained. RESULTS: 102 patients with CT scans both at the referring hospital and our center were identified. During patient transfer, e-ASPECTS declined by a median of 1 point (0-2). Functional outcome correlated with the change in e-ASPECTS (decline, n=54) (Spearman rs =0.322, 95% CI 0.131 to 0.482, p=0.001). The median image-to-image time was 149 min (IQR 113-190), but did not correlate with change in e-ASPECTS (p=0.754) and mRS score at 3 months (p=0.25). Preserved good collateral status assessed at the comprehensive stroke center was associated with better functional outcome (rs =-0.271, 95% CI -0.485 to -0.037, p=0.02). CONCLUSIONS: Patient transfer in a drip-and-ship network was associated with declines in e-ASPECTS associated with worse functional outcome. Image-to-image time did not influence this association, but worsening collateral status did.

Prediction of intracranial hemorrhages after mechanical thrombectomy of basilar artery occlusion.

BACKGROUND: Mechanical thrombectomy (MT) achieves high recanalization rates in basilar artery occlusion (BAO). A severe complication of MT in BAO is intracranial hemorrhage (ICH). Yet, knowledge of risk factors for ICH after MT in BAO is limited. OBJECTIVE: To evaluate clinical and procedural parameters of patients treated with MT owing to BAO to identify potential risk factors for ICH-in particular, symptomatic ICH (sICH), and assess their clinical relevance. METHODS: We conducted a retrospective analysis of 101 consecutive patients presenting with BAO, who were treated with MT in our centre. Important clinical and procedural parameters were analysed as possible predictors for any ICH and sICH according to the Heidelberg Bleeding Classification using univariate tests and multivariate logistic regressions. RESULTS: ICH occurred in 25 (24.8%) patients, with a total of 7 (6.9%) developing sICH. Treatment with glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors was independently associated with any ICH (OR=24.67, 95% CI 4.90 to 124.03) and sICH (OR=7.08, 95% CI 1.36 to 36.78). Also, a longer onset-to-recanalization time increased the risk of both any ICH (OR=1.17, 95% CI 1.07 to 1.31) and sICH (OR=1.22, 95% CI 1.08 to 1.42). Higher serum glucose levels were associated with a higher incidence of any ICH (OR=1.39, 95% CI 1.06 to 1.85) and a higher risk of a fatal outcome (OR=1.03, 95% CI 1.01 to 1.05). CONCLUSION: Administration of GPIIb/IIIa inhibitor during the course of MT of BAO was identified as an important risk factor in the development of any ICH and sICH.

Simplified selection criteria for patients with longer or unknown time to treatment predict good outcome after mechanical thrombectomy.

OBJECTIVE: To identify simplified selection criteria for mechanical thrombectomy (MT) in longer and unknown time windows. METHODS: Patients with large vessel occlusion (LVO) in the anterior circulation who underwent MT between January 2014 and November 2017 were identified from the local registry. Patients were selected for analysis if they met the current guideline recommendation for MT treatment except for time window (HERMES-like) and were divided according to time they were last seen well (LSW): LSW <6 hours or LSW >6 hours before MT. The primary endpoint, good outcome, was modified Rankin scale score 0-2 on day 90. Safety outcomes were mortality on day 90 and symptomatic intracranial hemorrhage (sICH). Univariate and multivariate analysis were performed for good outcome in HERMES-like patients. RESULTS: In total, 752 patients were identified and 390 patients (51.9%) fulfilled the HERMES-like criteria. Despite differences in baseline parameters, more diffusion-weighted imaging (DWI) (43.9% vs 11.3%, p<0.001) and fewer cases of thrombolysis (32.7% vs 77%, p<0.001), patients LSW >6 hours (n=107) did not differ in the primary and secondary endpoints: good outcome (44.9% vs 44.9%, p=1.0), mortality (14% vs 15.2%, p=0.87), and sICH (5.6% vs 6%, p=1.0). After multivariate regression analysis, independent predictors of good outcome remained: age, OR=0.96 (95% CI 0.95 to 0.98); National Institutes of Health Stroke Scale score, OR=0.92 (95% CI 0.89 to 0.96); Alberta Stroke Programme Early CT Score (ASPECTS), OR=1.26 (95% CI 1.06 to 1.49); general anesthesia, OR=0.2 (95% CI 0.04 to 0.99), and successful recanalization, OR=12 (95% CI 4.7 to 30.5); but not treatment time and DWI or CT perfusion at baseline. CONCLUSION: Patients with proven LVO in unknown and longer time windows may be selected for MT based on ASPECTS and clinical criteria.

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.

Endovascular stroke therapy may be safe in patients with elevated international normalized ratio.

INTRODUCTION: Endovascular therapy in acute ischemic stroke is safe and efficient. However, patients receiving oral anticoagulation were excluded in the larger trials. OBJECTIVE: To analyze the safety of endovascular therapy in patients with acute ischemic stroke and elevated international normalized ratio (INR) values. METHODS: Retrospective database review of a tertiary care university hospital for patients with anterior circulation stroke treated with endovascular therapy. Patients with anticoagulation other than vitamin K antagonists were excluded. The primary safety endpoint was defined as symptomatic intracranial hemorrhage (sICH; ECASS II definition). The efficacy endpoint was the modified Rankin scale (mRS) score after 3 months, dichotomized into favorable outcome (mRS 0-2) and unfavorable outcome (mRS 3-6). RESULTS: 435 patients were included. 90% were treated with stent retriever. 27 (6.2%) patients with an INR of 1.2-1.7 and 21 (4.8%) with an INR >1.7. 33 (7.6%) had sICH and 149 patients (34.3%) had a favorable outcome. Patients with an elevated INR did not have an increased risk for sICH or unfavorable outcome in multivariable analysis. The additional use of IV thrombolysis in patients with an INR of 1.2-1.7 did not increase the risk of sICH or unfavorable outcome. These results were replicated in a sensitivity analysis introducing an error of the INR of ±5%. They were also confirmed using other sICH definitions (Safe Implementation of Thrombolysis in Stroke (SITS), National Institute of neurological Disorders and Stroke (NINDS), Heidelberg bleeding classification). CONCLUSIONS: Endovascular therapy in patients with an elevated INR is safe and efficient. Patients with an INR of 1.2-1.7 may be treated with combined IV thrombolysis and endovascular therapy.

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 Intra-Arterial Thrombectomy within 72 Hours in a Patient with a Clear Contraindication for Intravenous Thrombolysis.

Introduction. Treating patients with acute ischemic stroke, proximal arterial vessel occlusion, and absolute contraindication for administering intravenous recombinant tissue plasminogen activator (rtPA) poses a therapeutic challenge. Intra-arterial thrombectomy constitutes an alternative treatment option. Materials and Methods. We report a case of a 57-year-old patient with concomitant gastric adenocarcinoma, who received three intra-arterial thrombectomies in 72 hours due to repeated occlusion of the left medial cerebral artery (MCA). Findings. Intra-arterial recanalization of the left medial cerebral artery was performed three times with initially good success. However, two days later, the right medial cerebral artery became occluded. Owing to the overall poor prognosis at that time and knowing the wishes of the patient, we decided not to perform another intra-arterial recanalization procedure. Conclusion. To our knowledge, this is the first case illustrating the use of repeated intra-arterial recanalization in early reocclusion of intracranial vessels.

To stent or not to stent: stent-protected percutaneous angioplasty versus endarterectomy post hoc analyses.

PURPOSE OF REVIEW: To summarize randomized controlled trials on endarterectomy and stenting of symptomatic carotid stenoses and identify factors that impact the decision for either therapeutic method. RECENT FINDINGS: Carotid endarterectomy is currently the standard method of secondary stroke prevention in patients with moderate-to-severe symptomatic carotid artery stenosis. Carotid artery stenting has emerged as a therapeutic alternative. The noninferiority to endarterectomy with respect to periprocedural safety has not been proven, but the long-term efficiency of stroke prevention after successful stenting is very similar, despite the observation that the rate of restenosis after stenting is significantly higher than after endarterectomy. Thus, the key difference between stenting and surgery is periprocedural safety. From subgroup analysis of the Stent-protected Percutaneous Angioplasty versus Endarterectomy data, it emerges that elderly patients are at higher than average periprocedural risk of ipsilateral stroke on the day of stenting but not if treated by surgery. This finding is an argument for catheter access problems through tortuous vessels with severe atherosclerosis in the proximal carotid artery of elderly patients as the source of periprocedural risk of stenting. SUMMARY: Carotid artery stenting for secondary stroke prevention is a method with unproven noninferiority of periprocedural safety but similar long-term efficiency compared to endarterectomy.