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.

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.

Echocardiography in acute stroke patients: a nationwide analysis in departments with certified stroke units in Germany.

BACKGROUND: Echocardiography is highly relevant in patients with ischemic stroke or TIA. Utilization of routine echocardiographic examinations [transthoracic (TTE) or transesophageal (TEE)] on stroke units remains however unknown. To representatively examine echocardiographic rates on stroke units in Germany and to evaluate structural factors that may influence the decision to conduct echocardiography. METHODS: A nationwide analysis was performed by using certification audit data of all primary and comprehensive stroke centers (pSC and cSC) in Germany. RESULTS: Structural and organizational requirements of 310 departments (cSCs: 42.6%) were extracted. Median TTE rate was 63.3% (IQR 39.3-80.8), median TEE rate 21.3% (IQR 16.4-29.5). A cardiological department on site was present in 74.2%, and they were associated with higher TEE rates. TTE rates decreased with increasing numbers of patients (p = 0.026). Likewise, TEE rates decreased with increasing numbers of patients (p = 0.006), mediated by departments with cSCs (p = 0.008 for cSCs vs p = 0.230 for pSCs). TTE rates were far more inhomogeneously distributed than TEE rates and higher in pSCs (p = 0.011). Overall, 12.9% of centers did not perform any echocardiographic examination in at least 50% of all stroke patients. CONCLUSION: More detailed recommendations regarding echocardiography should be included in future guidelines. Moreover, evaluating the impact of echocardiographic examinations on long-term prognosis in stroke patients should be focus of further evaluations.

Coping Strategies and Posttraumatic Growth Following Transient Ischemic Attack: A Qualitative Study.

A transient ischemic attack (TIA) is defined as a temporary neurological dysfunction due to focal brain ischemia. We aimed to identify common coping strategies and the possible occurrence of posttraumatic growth in TIA patients. Semistructured interviews were conducted with TIA patients three months after TIA. We asked the participants about possible changes in the aftermath of their TIA and their way of coping with said changes. All interviews were tape-recorded and subsequently transcribed verbatim. Thematic content analysis was performed to identify main categories and themes. Seventeen patients with a median age of 66 years completed the semistructured interviews. Qualitative content analysis revealed 332 single codes, from which the three main categories "impairments as a consequence of TIA", "coping strategies" and "posttraumatic growth" were generated. The main categories were further subdivided into seven categories and thirty-six themes. TIA patients may suffer from various physical impairments, which also involve medication side effects. Activating resources on the one hand, and avoiding negative thoughts and feelings on the other hand, were identified to be the relevant coping strategies in TIA patients. Posttraumatic growth seems to be a common phenomenon after TIA, which may have important implications for treatment and rehabilitation.

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).

Hyperdense Artery Sign in Patients With Acute Ischemic Stroke-Automated Detection With Artificial Intelligence-Driven Software.

Background: Hyperdense artery sign (HAS) on non-contrast CT (NCCT) can indicate a large vessel occlusion (LVO) in patients with acute ischemic stroke. HAS detection belongs to routine reporting in patients with acute stroke and can help to identify patients in whom LVO is not initially suspected. We sought to evaluate automated HAS detection by commercial software and compared its performance to that of trained physicians against a reference standard. Methods: Non-contrast CT scans from 154 patients with and without LVO proven by CT angiography (CTA) were independently rated for HAS by two blinded neuroradiologists and an AI-driven algorithm (Brainomix®). Sensitivity and specificity were analyzed for the clinicians and the software. As a secondary analysis, the clot length was automatically calculated by the software and compared with the length manually outlined on CTA images as the reference standard. Results: Among 154 patients, 84 (54.5%) had CTA-proven LVO. HAS on the correct side was detected with a sensitivity and specificity of 0.77 (CI:0.66-0.85) and 0.87 (0.77-0.94), 0.8 (0.69-0.88) and 0.97 (0.89-0.99), and 0.93 (0.84-0.97) and 0.71 (0.59-0.81) by the software and readers 1 and 2, respectively. The automated estimation of the thrombus length was in moderate agreement with the CTA-based reference standard [intraclass correlation coefficient (ICC) 0.73]. Conclusion: Automated detection of HAS and estimation of thrombus length on NCCT by the tested software is feasible with a sensitivity and specificity comparable to that of trained neuroradiologists.

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.

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.

Patient Pathways During Acute in-Hospital Stroke Treatment: A Qualitative Multi-Method Study.

Introduction: Patients experiencing acute ischemic stroke should access treatment as soon as possible to increase their chances for survival without severe disability. Given the increased complexity of stroke treatment from the provider and patient perspective, this study provides an overview of the pathways followed by stroke patients during in-hospital treatment. Methods: This qualitative study combined twenty-seven observations and fifteen staff interviews at a German comprehensive stroke center providing endovascular treatment ("EVT hospital"). Analysis was based on the COMIC Model for the comprehensive evaluation of complex health care interventions and a grounded theory approach. Results: The patient pathways during in-hospital treatment span the phases (1) admission to hospital, (2) receiving recanalization therapies, and (3) in-patient treatment. Before admission to the EVT hospital, interactions between staff members from the EVT hospital and patients take place as part of the telestroke consultations during which the EVT hospital's ED neurologist meets the patient via a video- and audio-based connection. During the second phase, when IVT and/or EVT are provided to the patient, three teams (ED, neuroradiology and ICU team) with direct patient interactions intersect at the angiography suite until mechanical recanalisation treatment ends and the patient is transferred to the SU or ICU. In the third phase, the patients are treated on the SU or ICU and staff members interact with them according to a pre-defined schedule as well as based on individual needs. Discussion: Our results show that most direct staff-patient interactions are focussed within one phase, with a smaller number of interactions extending to other phases, and no professional (group) with direct patient interactions cover more than two phases of the acute stroke pathway. Future research should investigate how the pathways described here are experienced from the patient perspective, including how the organisation of visible care processes may influence patient satisfaction. Findings can be translated to accessible patient information resources as well as input for digitalisation efforts, provider orientation and training.

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

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 was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. 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. 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.

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.

"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.

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.

Efficacy and safety of bridging thrombolysis initiated before transfer in a drip-and-ship stroke service.

OBJECTIVE: Data regarding the efficacy and safety of bridging thrombolysis (BT) initiated before transfer for evaluation of endovascular therapy is heterogeneous. We, therefore, analyse efficacy and safety of BT in patients treated within a drip-and-ship stroke service. METHODS: Consecutive adult patients suffering from acute ischaemic stroke and large-vessel occlusions (LVO) transferred to our comprehensive stroke centre for evaluation of endovascular therapy in 2017-2020 were identified from a local prospective stroke database and categorised according to BT and no-BT. BT was defined as intravenous thrombolysis initiated before transfer. LVO was assessed before and after transfer. Functional outcome before stroke and at 3 months using the modified Rankin scale (mRS) was determined. Excellent outcome was defined as mRS 0-1 or return to prestroke mRS. For safety analysis, intracranial haemorrhages and mortality at 3 months were analysed. Main analysis was limited to patients with anterior circulation stroke. RESULTS: Of N=714 patients, n=394 (55.2%) received BT. More patients in the BT group with documented LVO before transfer recanalised without endovascular therapy (n=46, 11.7%) than patients who did not receive BT before transfer (n=4, 1.3%, p<0.001). In multivariate analysis, BT was the strongest independent predictor of early recanalisation (adjusted OR 10.9, 95% CI 3.8 to 31.1, p<0.001). BT tended to be an independent predictor of an excellent outcome at 3 months (adjusted OR 1.38, 95% CI 0.97 to 1.96, p=0.077). There were no differences in safety between the BT and no-BT groups. CONCLUSIONS: BT initiated before transfer was a strong independent predictor of early recanalisation.

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 .

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.

PURPOSE: The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS: All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE: Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS: This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.

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.