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An abstract of the article∣Cerebral Microbleeds After Carotid Revascularisation: A Prospective MRI Study,∣by L.H. Bonati, I. Jongen, S. Wetzel, W. Mali, S. Engelter and M.M. Brown is presented.

Background: Spontaneous supratentorial intracerebral hemorrhage is the deadliest form of stroke with mortality rates over 50%. Currently, no sufficiently effective treatment to improve both mortality and functional outcome rates exists. However, it seems that minimally invasive surgery, especially endoscopic surgery, might be beneficial in improving survival and functional outcome rates, yet large confirmatory studies thereof are lacking. The aim of this trial is to compare whether early minimally invasive endoscopic surgery leads to improved functional outcome rates compared to the best medical treatment., Methods: This is a prospective, parallel-arm, outcome assessor blinded multicenter trial across Switzerland. Endoscopic surgery will be compared to the best medical treatment in a 1:1 randomization over a total time of 12 months. The primary outcome is defined as improved functional outcome (mRS < 3) after 6 months; secondary outcomes include mortality and morbidity rates as well as patient reported outcomes and the temporal evolution of serum biomarkers for brain damage., Discussion: Currently, large, randomized trials assessing the role and potential effect of early endoscopic surgery in intracerebral hemorrhage are lacking. Potential practical and methodological issues faced in this trial are patient enrollment, adherence to the hematoma evacuation technique used, potential patient cross-over, and the adaptive Bayesian statistical design. Nonetheless, this trial would be among the first to research the effects of early minimally invasive endoscopic surgery for SSICH and can provide class I evidence for future treatment options in intracerebral hemorrhage., Trial Registration: ClinicalTrials.gov NCT05681988. Registered on January 3, 2023., (© 2024. The Author(s).)

Introduction: Atrial fibrillation (AF) poses a significant risk of stroke. Left atrial appendage occlusion (LAAO) is an alternative for patients with contraindications to oral anticoagulation (OAC) or with high risk of bleeding. This study aims to compare the outcomes of LAAO versus conventional stroke prevention in high-risk AF-patients., Methods: This secondary analysis incorporates data from the prospective Swiss-AF and Beat-AF cohorts, and the Zurich LAAO Registry. Cardinality matching was performed to create two comparable cohorts: conventional treatment (92% OAC) and LAAO. The primary endpoint was a composite of stroke, cardiovascular (CV) death, and clinically relevant bleeding. Kaplan-Meier method with competing risk analysis was used., Results: Each group included 468 patients (age 76.4 [70.5, 82.0] years, 33% female). The LAAO group exhibited higher baseline bleeding risk (HAS BLED 2.0 [1.0-3.0] versus 3.0 [3.0-4.0]; p < 0.001). Median follow-up time: 6.0 (4.7-7.0) years in conventional treatment group and 4.0 (1.5-6.1) in LAAO group. No significant difference in the primary composite endpoint (HR 0.87, 95% CI: 0.72-1.06, p = 0.18), stroke risk (HR 1.14, 95% CI: 0.66-1.97, p = 0.64), or CV mortality (HR 1.08, 95% CI: 0.82-1.42, p = 0.60) was observed between groups. LAAO correlated with a significantly lower risk of clinically relevant bleeding (HR 0.61, 95% CI: 0.47-0.80, p < 0.001)., Conclusion: In this cardinality matched analysis with long-term follow-up, LAAO showed similar stroke and CV death rates but lower clinically relevant bleeding risk compared to conventional therapy in high-risk AF-patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Automated CT perfusion (aCTP) is commonly used to select patients with anterior circulation large vessel occlusion (aLVO) for endovascular treatment (EVT). The equivalence of visually assessed Non-contrast CT Alberta Stroke Program Early CT Scores (ASPECTS) and aCTP based selection in predicting favorable functional outcomes remains uncertain., Patients and Methods: Retrospective multicenter study of adult aLVO patients from the Swiss Stroke Registry (2014-2021) treated with EVT or best medical treatment 6-24 h after stroke onset. We assessed ASPECTS on non-contrast CT visually and ischemic core volumes on aCTP, defining ASPECTS 0-5 and aCTP CBF < 30% volumes ⩾50 mL as large ischemic cores. We used logistic regression to explore the association between CT modalities and favorable functional outcomes (modified Rankin Scale [mRS] score shift toward lower categories) at 3 months. Receiver operating characteristic (ROC) curve analysis compared the predictive accuracy of visually assessed ASPECTS and aCTP ischemic core for favorable outcomes (mRS 0-2) at 3 months., Results: Of 210 patients, 11.4% had ASPECTS 0-5, and 12.9% aCTP core volumes ⩾50 mL. Within the same model, ASPECTS but not aCTP core volumes were associated with favorable outcomes (ASPECTS: acOR 1.85, 95%CI 1.27-2.70, p  = 0.001). The ROC curve analyses showed comparable diagnostic accuracy in predicting favorable functional outcomes (mRS 0-2) at 3 months (ROC areas: ASPECTS 0.80 [95%CI 0.74-0.86] vs aCTP core 0.79 [95%CI 0.72-0.85])., Discussion and Conclusion: In patients with aLVO, visually assessed ASPECTS showed at least comparable accuracy to automatically generated CTP core volumes in predicting functional outcomes at 3 months., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RS received personal grants from UCB-pharma and holds stocks from Novartis, Roche, Alcon, and Johnson&Johnson. MK received funding form the Swiss National Science Foundation, the Swiss Heart Foundation, and USZ-foundation, and received honoraria and consulting fees from Astra Zeneca and BMS/Pfizer, and in-kind contributions from BRAHMS Termofisher Scientific, Roche Diagnostics. LHB received personal fees from Claret Medical and InnovHeart. GMDM received speaker honoraria from Medtronic. The remaining authors report no conflicts relevant to this study.

Randomized trials in stroke often focus on outcomes beyond a single clinical event. Trials of stroke prevention commonly use composite outcomes that include multiple components (eg, death, stroke, or myocardial infarction). A major limitation is that all events count equally but may differ markedly in terms of clinical severity. Trials in acute stroke often use ordinal outcomes or scale scores. Limitations include the requirement for statistical assumptions and the difficulty of handling the competing risk of death. We introduce the win ratio as an alternative method. It works by placing components of a composite into a hierarchy, whereby clinically more important outcomes take priority over less important ones. We illustrate how it works using data from 2 major stroke trials: the ICSS (International Carotid Stenting Study, a trial in stroke prevention) and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Potential benefits of the win ratio approach include the possibility to (1) emphasize the clinically most important outcomes, (2) combine components of different outcome types into a composite (eg, a mixture of time-to-event, continuous, and categorical), and (3) naturally handle the competing risk of death in analyses of quantitative outcomes. The win ratio will be used in the upcoming analysis of the ECST-2 (Second European Carotid Surgery Trial), which has a hierarchical primary outcome of (1) time to perioperative death, fatal stroke, or fatal myocardial infarction (most important); (2) time to nonfatal stroke; (3) time to nonfatal myocardial infarction (excluding silent infarcts); and (4) new silent cerebral infarct on brain imaging (least important). The win ratio provides a useful clinically relevant method for analyzing trial outcomes. It has some advantages over conventional methods, and we recommend its wider application in future stroke trials.

Objectives: To determine the prevalence and distribution of intracranial vessel occlusion identified on computed tomography (CT) or magnet resonance (MR) angiography and to explore its association with functional outcome in patients with atrial fibrillation (AF) and ischemic stroke., Methods: Multicenter cohort study enrolling consecutive patients with AF with imaging-confirmed ischemic stroke who underwent CT- or MR-angiography on admission (2014-2022). Multivariable regression was used to explore the association between intracranial vessel occlusion and poor functional outcome (modified Rankin Scale score 3-6) at 90 days., Results: The analysis included 10,164 patients (median age 81.5 years, 47.8% female, median National Institutes of Health Stroke Scale score on admission 6; 14.7% on a vitamin K antagonist [VKA], 27.5% on a direct oral anticoagulant [DOAC], 57.8% not receiving oral anticoagulation). Angiography showed intracranial vessel occlusion in 5,190 patients (51.1%), affecting the anterior cerebral circulation in 87.4%. Overall, 29.2% and 29.4% of patients received thrombolysis and mechanical thrombectomy, respectively. The proportion of patients with poor functional outcome at 90 days was 60.6% and 42.7% in those with and without vessel occlusion, respectively. In multivariable analyses, vessel occlusion was associated with poor functional outcome (adjusted odds ratio [aOR]: 1.95, 95% confidence interval [CI]: 1.71-2.22) with consistent results in subgroups according to oral anticoagulation use (VKA, aOR: 1.98, 95% CI: 1.40-2.80; DOAC, aOR: 2.35, 95% CI: 1.83-3.03; none, aOR: 1.76, 95% CI: 1.49-2.09)., Interpretation: Intracranial vessel occlusion is common in patients with AF with ischemic stroke, mainly affects the anterior circulation and is associated with poor functional outcome. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated., Patients and Methods: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades., Results: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group., Discussion and Conclusion: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MK received speaker honoraria from Medtronic. GMK is on a scientific advisory board of Bayer AG. CWC is member of the Medical and Scientific Advisory Boards of iSchemaView. LHB received personal fees from Claret Medical and InnovHeart. GMDM received speaker honoraria from Medtronic. The remaining authors report no conflicts of interests relevant to this study.

Background: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system., Objective: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients., Methods: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism., Results: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint., Conclusion: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients., Competing Interests: Disclosures Dr Beer reports grants from the Swiss National Foundation of Science, The Swiss Heart Foundation, and Bayer; and lecture fees from Sanofi Aventis and Amgen, to the institution outside the submitted work. Dr Blum has received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, all for work outside the submitted study. Dr Bonati has received an unrestricted research grant from AstraZeneca; consultancy or advisory board fees or speaker honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical; and travel grants from AstraZeneca and Bayer, outside the submitted work. Dr Conen received consultancy fees from Roche Diagnostics and Trimedics; and speaker fees from Servier and BMS/Pfizer, outside the submitted work. Dr Kühne received personal fees from Daiichi Sankyo and grants from the Swiss National Science Foundation, Swiss Heart Foundation, Foundation for CardioVascular Research Basel, Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo, outside the submitted work. Dr Krisai has speaker fees from BMS/Pfizer, outside the submitted work. Dr Müller reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, Zoll, and Bristol Myers Squibb; consultant fees from Biosense Webster, Medtronic, Abbott/St. Jude Medical, and Biotronik, outside the submitted work. Dr Moschovitis has received advisory board and/or speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis, and Vifor, outside the submitted work. Dr Osswald received research grants from the Swiss National Science Foundation and Swiss Heart Foundation, Foundation for CardioVascular Research Basel, and F. Hoffmann-La Roche Ltd.; and educational and speaker grants from F. Hoffmann-La Roche Ltd., Bayer, Novartis, Sanofi, AstraZeneca, Daiichi-Sankyo, and Pfizer, outside the submitted work. Dr Reichlin has recieved research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support funds; speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Farapulse, Medtronic, Pfizer-,BMS and Roche; and support for his institution’s fellowship program from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific, and Medtronic for work, outside the submitted study. Dr Zuern has received funding from the “Freiwillige Akademische Gesellschaft Basel”; and personal fees from Cardiomatics, outside the submitted work. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) as a result of iodinated contrast media (CM) has been linked to CM-induced renal ischemia and toxic effects on endothelial cells (EC). The recombinant human C1 inhibitor (rhC1INH) has been shown to influence EC activation., Methods: Secondary analysis of 74/77 (96%) participants of a double-blind, randomized, and placebo-controlled study that assessed the effect of rhC1INH on AKI. E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), and CC-chemokin-ligand-5 (CCL5) were determined in frozen blood samples over 48 h and analyzed according to the treatment group and renal outcomes., Results: The mean age was 76.7 years, and 37 patients each received rhC1INH and placebo, respectively. In the entire study population, minor differences in median EC activation markers/CCL5 concentrations during the first 48 h compared to baseline were observed (e.g., E-selectin 27.5 ng/mL at baseline vs. 29.7 ng/mL on day 1, CCL5: 17.7 ng/mL at baseline vs. 32.2 ng/mL on day 2). Absolute changes in ICAM-1/E-selectin concentrations correlated with a higher peak change in urinary NGAL concentrations. However, AKI was not associated with significant changes in EC markers/CCL5. Last, no significant differences in serum concentrations of EC activation markers/CCL5 were evident between the placebo and the rhC1INH group., Conclusions: CM administration during coronary angiography only mildly activated ECs within the first 48 h, which does not explain subsequent AKI. The administration of rhC1INH was not associated with a reduction of EC activation or CCL5.

Introduction: There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies., Methods: Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status., Results: Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAA vs non-LAA = 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51])., Conclusion: The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Background: Electrical cardioversion (ECV) is frequently performed in symptomatic atrial fibrillation., Objective: This study aimed to assess the association of ECV with infarcts on brain magnetic resonance imaging (bMRI) and clinical outcomes., Methods: The Swiss Atrial Fibrillation Cohort Study included 2386 patients; 1731 patients were evaluated by bMRI. ECVs were recorded by questionnaire. Patients were assigned to categories by number of ECVs performed before enrollment (0, 1, ≥2). A bMRI study was conducted at baseline and after 2 years (n = 1227) and analyzed for large noncortical or cortical infarcts and small noncortical infarcts. Clinical outcomes were recorded during follow-up. Associations of ECV and outcome measures were assessed by multivariate analyses., Results: There was no independent association between the number of ECVs and infarct prevalence (large noncortical or cortical infarcts and small noncortical infarcts) on baseline bMRI (ECV 1 vs 0: odds ratio [OR], 0.95 [95% CI, 0.68-1.24]; ECV ≥2 vs 0: OR, 1.04 [0.72-1.44]) or between ECVs performed during follow-up and new infarcts on bMRI at 2 years (OR, 1.46 [0.54-3.31]). ECVs were not associated with overt stroke or transient ischemic attack (ECV 1 vs 0: hazard ratio [HR], 1.36 [0.88-2.10]; ECV ≥2 vs 0: HR, 1.53 [0.94-2.48]), hospitalization for heart failure (ECV 1 vs 0: HR, 1.06 [0.82-1.37]; ECV ≥2 vs 0: HR, 1.03 [0.77-1.38]), or death (ECV 1 vs 0: HR, 0.90 [0.70-1.15]; ECV ≥2 vs 0: HR, 0.91 [0.69-1.20])., Conclusion: There was no association between ECV performed before enrollment and cerebral infarcts on baseline bMRI or between ECV performed during follow-up and new infarcts at 2 years. Moreover, ECV was not associated with clinical events., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The patho-psychological mechanisms of persistent postural-perceptual dizziness (PPPD) appear to be very complex, and a multimodal, multidisciplinary approach is suggested for treating patients with PPPD. The aim of this review was to provide a comprehensive overview of non-pharmacological treatments and their comparative effectiveness in patients with PPPD., Methods: Scopus, Web of Science, PsycINFO, Medline, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov were searched in April 2022 with a search update in August 2023. Only randomized controlled trials (RCTs) were included. There was no restrictions regarding publication date. Two reviewers independently identified eligible trials, extracted data, double-checked all extracted information from the included articles and assessed the risk of bias using the Cochrane risk of bias tool. A qualitative synthesis was performed, considering methodological heterogeneity between trials. Finally, an effect size analysis was performed for each treatment comparison. The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95%CI) were calculated for each trial using Review Manager 5.4., Results: Thirteen RCTs (618 patients with moderate or mild dizziness) out of 1,362 references describing seven different non-pharmacological comparisons were selected. Nine trials included patients with PPPD, and four trials included patients with functional dizziness. The trials used different interventions that were classified as: (1) psychotherapeutic interventions (cognitive behavioral therapy, patient education), (2) physiotherapeutic interventions/training (vestibular rehabilitation, optokinetic stimulation), (3) stimulation procedures (vagus nerve stimulation, transcranial direct current stimulation) and (4) device application (visual desensitization using personalized glasses). However, most of the trials investigated the effects of single interventions, rather than multimodal interdisciplinary treatment of patients with PPPD. The SMD for dizziness handicap and severity was between 0.04 and 0.52 in most trials. In one trial using visual desensitization, the SMD was 1.09 (strong effect on the severity of dizziness) and 1.05 (strong effect on dizziness handicap)., Discussion: Several individual interventions have shown benefits in the treatment of patients with PPPD with small to moderate effects. However, the multimodal treatment or a combination of vestibular rehabilitation with visual desensitization, cognitive behavioral therapy including patient education, and medication support should be further investigated. Future trials should include a large sample size with severe dizziness, and provide a longer follow-up period., Clinical Trial Registration: PROSPERO CRD42022320344., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Suica, Behrendt, Ziller, Gäumann, Schädler, Hilfiker, Parmar, Gerth, Bonati and Schuster-Amft.)

Research to improve and expand treatment options for motor impairment after stroke remains an important issue in rehabilitation as the reduced ability to move affected limbs is still a limiting factor in the selection of training content for stroke patients. The combination of action observation and peripheral nerve stimulation is a promising method for inducing increased excitability and plasticity in the primary motor cortex of healthy subjects. In addition, as reported in the literature, the use of action observation and motor imagery in conjunction has an advantage over the use of one or the other alone in terms of the activation of motor-related brain regions. The aim of the pilot study was thus to combine these findings into a multimodal approach and to evaluate the potential impact of the concurrent application of the three methods on dexterity in stroke patients. The paradigm developed accordingly was tested with 10 subacute patients, in whom hand dexterity, thumb-index pinch force and thumb tapping speed were measured for a baseline assessment and directly before and after the single intervention. During the 10-min session, patients were instructed to watch a repetitive thumb-index finger tapping movement displayed on a monitor and to imagine the sensations that would arise from physically performing the same motion. They were also repeatedly electrically stimulated at the wrist on the motorically more affected body side and asked to place their hand behind the monitor for the duration of the session to support integration of the displayed hand into their own body schema. The data provide a first indication of a possible immediate effect of a single application of this procedure on the dexterity in patients after stroke., (© 2024. The Author(s).)

Objective: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment., Methods: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing., Results: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation., Interpretation: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation., Methods: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months., Results: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%))., Conclusions: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future., Competing Interests: Competing interests: MBo: personal fees from AstraZeneca, a company that produces Andexanet alfa (a specific reversal agent for factor Xa-inhibitor-associated ICH, discussed in this study). SW: consultancy fees from Bayer, a company that produces Rivaroxaban (a DOAC discussed in this study). BV: personal fees from Pfizer AG/Bristol-Myers Squibb SA and Bayer AG, producesr of Apixaban and Rivaroxaban, two drugs discussed in this study. DJS: grants from Alexion/AstraZeneca, producer of andexanet alfa discussed in this study. Personal fees from Bayer, producer of Rivaroxaban, discussed in this study. Consultancy fees from VarmX (producer of VarmX, a compound under development for the treatment of FXaI-associated bleeding). All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The majority of stroke survivors experience long-term impairments. Regular physical activity and other lifestyle modifications play an important role in rehabilitation. Outpatient rehabilitation using telemedicine might be suitable to improve functional ability and long-term secondary prevention. The Strokecoach Intervention Program (SIP, Strokecoach GmbH, Cologne, Germany) comprises training, coaching and monitoring with the aim of improving or at least maintaining functional independence and preventing further stroke through more targeted physical activity. The SIP is provided as blended care, which refers to the integrated and coordinated delivery of healthcare services that combines traditional in-person interactions with technology-mediated interventions, optimizing the use of both face-to-face and virtual modalities to enhance patient outcomes., Objective: The aim of this study was to evaluate the acceptance of the SIP by the participants and its practical application, as well as to obtain initial indications of effects of the SIP on the basis of patient-related outcome measures, blood pressure measurements and recording of physical activity in parallel with the intervention., Methods: Data from individuals with stroke participating in the SIP were analyzed retrospectively. Within the SIP, participants received an application-based training program, were instructed to measure their blood pressure daily and to wear an activity tracker (pedometer). During the intervention period of either 6 or 12 weeks, the participants were supported and motivated by a personal coach via a messenger application. The primary outcomes of the analysis were recruitment, acceptance of and satisfaction with the SIP. Secondary outcomes included functional measures, mobility and health-related quality of life., Results: A total of 122 individuals with stroke could be recruited for the SIP. A total of 96 out of 122 were able to start the program (54% female, mean age 54.8 (SD = 13.1), 6.1 (SD = 6.6) years after stroke onset) and 88 completed the SIP. Participants wore the activity tracker on 66% and tracked their blood pressure on 72% of their intervention days. A further analyzed subgroup of 38 participants showed small improvements in patient-reported outcomes such as health-related quality of life (SF-36) with an increase of 12 points in the subdomain mental health, vitality (12.6) and physical functioning (9.1). However, no statistically significant improvements were found in other performance-based measures (Timed Up and Go test, gait speed)., Conclusions: This study showed that a blended therapy approach for stroke survivors with mild to moderate impairments in the chronic phase is feasible and was highly accepted by participants, who benefitted from the additional coaching.

Background and Objectives: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH., Methods: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses., Results: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes., Discussion: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

Background: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features., Objectives: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score., Methods: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports., Results: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories., Conclusions: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists., Competing Interests: Funding Support and Author Disclosures The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government. The identification of specific products or scientific instrumentation does not constitute endorsement or implied endorsement on the part of the author, Department of Defense, or any component agency. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Optimizing health-related quality of life (HRQoL) is an important aim of atrial fibrillation (AF) treatment. Little is known about patients' long-term HRQoL trajectories and the impact of patient and disease characteristics. The aim of this study was to describe HRQoL trajectories in an observational AF study population and in clusters of patients with similar patient and disease characteristics. Methods and Results We used 5-year follow-up data from the Swiss-Atrial Fibrillation prospective cohort, which enrolled 2415 patients with prevalent AF from 2014 to 2017. HRQoL data, collected yearly, comprised EuroQoL-5 dimension utilities and EuroQoL visual analog scale scores. Patient clusters with similar characteristics at enrollment were identified using hierarchical clustering. HRQoL trajectories were analyzed descriptively and with inverse probability-weighted regressions. Effects of postbaseline clinical events were additionally assessed using time-shifted event variables. Among 2412 (99.9%) patients with available baseline HRQoL, 3 clusters of patients with AF were identified, which we characterized as follows: "cardiovascular dominated," "isolated symptomatic," and "severely morbid without cardiovascular disease." Utilities and EuroQoL visual analog scale scores remained stable over time for the full population and the clusters; isolated symptomatic patients showed higher levels of HRQoL. Utilities were reduced after occurrences of stroke, hospitalization for heart failure, and bleeding, by -0.12 (95% CI, -0.18 to -0.06), -0.10 (95% CI, -0.13 to -0.08), and -0.06 (95% CI, -0.08 to -0.04), respectively, on a 0 to 1 utility scale. Utility of surviving patients returned to preevent levels 4 years after heart failure hospitalization; 3 years after bleeding; and 1 year after stroke. Conclusions In patients with prevalent AF, HRQoL was stable over time, irrespective of baseline patient characteristics. Clinical events of hospitalization for heart failure, stroke, and bleeding had only a temporary effect on HRQoL.

Purpose: Carotid intraplaque hemorrhage (IPH) on MRI predicts stroke. Magnetization-prepared rapid acquisition gradient (MP-RAGE) is widely used to detect IPH. CE-MRA is used routinely to assess stenosis. Initial studies indicated that IPH can be identified on mask images of CE-MRA, while Time-of-Flight (TOF) images were reported to have high specificity but lower sensitivity. We investigated the diagnostic accuracy of detecting IPH on mask images of CE-MRA and TOF., Methods: Thirty-six patients with ≥ 50% stenosis enrolled in the ongoing 2nd European Carotid Surgery Trial underwent carotid MRI. A 5-point quality score was used. Inter-observer agreement between two independent readers was determined. The sensitivity and specificity of IPH detection on mask MRA and TOF were calculated with MP-RAGE as a reference standard., Results: Of the 36 patients included in the current analysis, 66/72 carotid arteries could be scored. The inter-observer agreements for identifying IPH on MP-RAGE, mask, and TOF were outstanding (κ: 0.93, 0.96, and 0.85). The image quality of mask (1.42 ± 0.66) and TOF (2.42 ± 0.66) was significantly lower than MP-RAGE (3.47 ± 0.61). When T1w images were used to delineate the outer carotid wall, very high specificities (>95%) of IPH detection on mask and TOF images were found, while the sensitivity was high for mask images (>81%) and poor for TOF (50-60%). Without these images, the specificity was still high (>97%), while the sensitivity reduced to 62-71%., Conclusion: Despite the lower image quality, routinely acquired mask images from CE-MRA, but not TOF, can be used as an alternative to MP-RAGE images to visualize IPH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA 2 DS 2 -VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up., Methods: Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA 2 DS 2 -VASc score., Results: We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45-2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20-2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11-2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02-2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00-1.86]), and hFABP (heart-type fatty acid-binding protein; aOR, 0.48 [95% CI, 0.31-0.73]). Overall performance and discrimination of the new model was superior to that of the CHA 2 DS 2 -VASc score (C statistic, 0.82 [95% CI, 0.77-0.87] versus 0.64 [95% CI, 0.58-0.70])., Conclusions: In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures., Competing Interests: Disclosures Dr De Marchis reports honoraria by Bayer, Pfizer, Medtronic and a Grant from Novartis unrelated to the present work. Industry payments are made to the research fund of the University Hospital Basel. Dr Aeschbacher reports speaker fees from Roche Diagnostics. Dr Reichlin reports consultant honoraria/grants from Abbott Laboratories, Biosense Webster, Inc, Biotronik, Boston Scientific Corporation, and Medtronic. Dr Moschovitis has received consultant fees for taking part to advisory boards from Novartis, Boehringer Ingelheim, Bayer, Astra Zeneca and Daiichi Sankyo, all outside of the submitted work. Dr Wuerfel is employed at Roche. Dr Lyrer reports honoraria from Bayer, Biogen, Boehringer Ingelheim, Pfizer – all unrelated to the present work – and grants from the Swiss National Science Foundation and University Hospital Basel (intramural grant). Dr Fischer reports grant/contracts from Alexion, Biogen, Medtronic Vascular, Penumbra, Phenox, Rapid Medical, as well as support from Stryker and CSL Behring Foundation for Research and Advancement of Patient Health. Dr Conen reports consultation fees from Roche Diagnostics and Trimedics, as well as speaker fees from Servier and Pfizer. Dr Ziegler is employed at Roche Diagnostics International. Dr Kühne reports personal fees from Bayer, personal fees from Böhringer Ingelheim, personal fees from Pfizer Bristol-Myers Squibb (BMS), personal fees from Daiichi Sankyo, personal fees from Medtronic, personal fees from Biotronik, personal fees from Boston Scientific, personal fees from Johnson&Johnson, personal fees from Roche, grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik, grants from Daiichi Sankyo. Dr Bonati reports honoraria from Amgen, AstraZeneca, Bayer, BMS, Claret Medical, grants from the Swiss National Science Foundation, Swiss Heart Foundation, University of Basel, and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung. The other authors report no conflicts.

Background: Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events., Methods: A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-)., Results: The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group., Conclusions: Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: ISRCTN 25337470., Competing Interests: Disclosures Dr van der Lugt received research grants from GE Healthcare, Siemens Healthineers, Cerenovus, Medtronic USA, Inc and Stryker Corporation, and Philips Healthcare all paid to the institution. Dr Bonati has received grants from Swiss National Science Foundation, University of Basel, Swiss Heart Foundation, AstraZeneca and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung; personal fees from Amgen, Bayer, Bristol-Myers Squibb, Claret Medical, and InnovHeart; and nonfinancial support from AstraZeneca and Bayer. All other authors have reported that they have no relationships relevant to the contents of this article to disclose.

Background: Persistent postural-perceptual dizziness (PPPD) is a functional disorder of the nervous system and currently one of the most common types of chronic dizziness. Currently existing questionnaires do not fully assess patients' specific symptoms of PPPD. The Japanese Niigata PPPD Questionnaire (NPQ) was recently developed following consensus-based diagnosis criteria. The aim of this study was to translate it into German, evaluate its content with the help of experts and patients and, if necessary, revise the original version to allow for a comprehensive assessment of patients' PPPD-related symptoms., Methods: A 3-round expert Delphi survey and semi-structured patient interviews were conducted. 28 experts from Switzerland, Germany and Austria working in hospitals or outpatient centres were asked to complete a first questionnaire on various aspects of PPPD, on the translated, original NPQ and their own related experiences (Round one), a second questionnaire with statements regarding PPPD they could agree or disagree with using a 6-point Likert-scale (Round two), and a third survey to finally reach a consensus on statements to be integrated into the NPQ. In addition, eleven patients (mean age of 64.6±12.6 years; 6 females) were selected according to the criteria for the diagnosis of PPPD proposed by the Bárány Society and participated in a semi-structured interview asking for their opinion on the content of the original NPQ. All collected data were analysed using a descriptive evaluation and a qualitative content analysis based on verbatim transcripts., Results: Seven new items were added to the NPQ based on expert and patient comments and ratings. Its revised version (NPQ-R) comprises 19 items divided into five subscales using a 7-point Likert-scale with two additional subscales relating to associated symptoms and symptom behaviour in PPPD. The new maximal score is 114 points compared to 72 for the NPQ., Conclusion: The NPQ-R is the first patient-reported outcome measurement for patients with PPPD in German. It should help to provide a comprehensive assessment of the intensity of PPPD in affected patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Behrendt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce., Methods: We used prospectively obtained data from an observational registry (Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed., Results: Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR [95% CI] 1.64 [1.11, 2.40], p  = 0.017) and recurrent IS (aHR 2.96 [1.65, 5.35 ], p  < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause., Conclusion: In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients., Clinical Trial Registration: NCT03826927.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To assess the associations of chocolate consumption with neurocognitive function, brain lesions on magnetic resonance imaging (MRI), and cardiovascular outcome in patients with atrial fibrillation (AF)., Methods: We analysed data from patients of two prospective multicentre Swiss atrial fibrillation cohort studies (Swiss-AF) and (BEAT-AF). Assessments of MRI findings and neurocognitive function were performed only in the Swiss-AF population (in 1727 of 2415 patients [71.5%] with a complete data set), as patients enrolled in BEAT-AF were not systematically evaluated for these outcomes. Otherwise, the two cohorts had an equivalent set of clinical assessments. Clinical outcome analysis was performed in 3931 patients of both cohorts. Chocolate consumption was assessed by questionnaire. Patients were categorised as no/low chocolate consumption (No/Low-Ch) ≤1 servings/week, moderate chocolate consumption (Mod-Ch) >1-6 servings/week, and high chocolate consumption (High-Ch) >6 servings/week, respectively. Brain lesions were evaluated by MRI. Assessment of cognitive function was performed by neurocognitive functional testing and included global cognition measurement with a cognitive construct score. Cerebral MRI and cognition were evaluated at baseline. Cross-sectional associations between chocolate consumption and MRI findings were analysed by multivariate logistic regression models and associations with neurocognitive function by multivariate linear regression models. Clinical outcome events during follow-up were recorded and assessed by a clinical event committee. The associations between chocolate consumption and clinical outcomes were evaluated by Cox regression models. The median follow-up time was 6 years., Results: Chocolate consumption was not associated with prevalence or volume of vascular brain lesions on MRI, nor major adverse cardiac events (ischaemic stroke, myocardial infarction, cardiovascular death). However, No/Low-Ch was independently associated with a lower cognitive construct score compared to Mod-Ch (No/Low-Ch vs. Mod-Ch: coeff. -0.05, 95% CI -0.10-0), whereas other neurocognitive function tests were not independently associated with chocolate consumption categories. In addition, there was a higher risk of heart failure hospitalisation (No/Low-Ch vs. Mod-Ch: HR 1.24, 95% CI 1.01-1.52) and of all-cause mortality (No/Low-Ch vs. Mod-Ch: HR 1.29, 95% CI 1.06-1.58) in No/Low-Ch compared to Mod-Ch. No significant associations with the evaluated outcomes were observed when High-Ch was compared to Mod-Ch., Conclusion: While chocolate consumption was not associated with MRI findings and major adverse cardiac events in an atrial fibrillation population, No/Low-Ch was associated with a lower cognitive construct score, higher risk of heart failure hospitalisation and increased all-cause mortality compared to Mod-Ch., Clinicaltrials: gov Identifier: NCT02105844.

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

Introduction: It is suggested that eye movement recordings could be used as an objective evaluation method of motor imagery (MI) engagement. Our investigation aimed to evaluate MI engagement in patients after stroke (PaS) compared with physical execution (PE) of a clinically relevant unilateral upper limb movement task of the patients' affected body side., Methods: In total, 21 PaS fulfilled the MI ability evaluation [Kinaesthetic and Visual Imagery Questionnaire (KVIQ-10), body rotation task (BRT), and mental chronometry task (MC)]. During the experiment, PaS moved a cup to distinct fields while wearing smart eyeglasses (SE) with electrooculography electrodes integrated into the nose pads and electrodes for conventional electrooculography (EOG). To verify MI engagement, heart rate (HR) and oxygen saturation (SpO 2 ) were recorded, simultaneously with electroencephalography (EEG). Eye movements were recorded during MI, PE, and rest in two measurement sessions to compare the SE performance between conditions and SE's psychometric properties., Results: MI and PE correlation of SE signals varied between r = 0.12 and r = 0.76. Validity (cross-correlation with EOG signals) was calculated for MI ( r = 0.53) and PE ( r = 0.57). The SE showed moderate test-retest reliability (intraclass correlation coefficient) with r = 0.51 (95% CI 0.26-0.80) for MI and with r = 0.53 (95% CI 0.29 - 0.76) for PE. Event-related desynchronization and event-related synchronization changes of EEG showed a large variability. HR and SpO 2 recordings showed similar values during MI and PE. The linear mixed model to examine HR and SpO 2 between conditions (MI, PE, rest) revealed a significant difference in HR between rest and MI, and between rest and PE but not for SpO 2 . A Pearson correlation between MI ability assessments (KVIQ, BRT, MC) and physiological parameters showed no association between MI ability and HR and SpO 2 ., Conclusion: The objective assessment of MI engagement in PaS remains challenging in clinical settings. However, HR was confirmed as a reliable parameter to assess MI engagement in PaS. Eye movements measured with the SE during MI did not resemble those during PE, which is presumably due to the demanding task. A re-evaluation with task adaptation is suggested., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gäumann, Aksöz, Behrendt, Wandel, Cappelletti, Krug, Mörder, Bill, Parmar, Gerth, Bonati and Schuster-Amft.)

Background: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH., Methods: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis., Results: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P =0.40). There was a signal for interaction with onset-to-treatment time ( P interaction =0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P =0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P =0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation., Conclusions: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Background: Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk., Methods: Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation., Results: Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death., Conclusion: Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: The DEFUSE-3 and DAWN trials showed that mechanical thrombectomy (MT) improves the outcome of selected patients with anterior circulation large vessel occlusions (LVO) up to 24 h after stroke onset. However, it is unknown whether only those patients fulfilling the trial inclusion criteria benefit, or whether benefit is seen in a broader range of patients presenting between 6 and 24 h., Aims: We determined whether fulfilling the DEFUSE-3 and DAWN selection criteria affects outcomes in MT patients in clinical practice., Methods: We reviewed adult patients with LVO treated with MT between 6 and 24 h after stroke onset at five Swiss stroke centers between 2014 and 2021. We compared two groups: (1) patients who satisfied neither DEFUSE-3 nor DAWN criteria (NDND) and (2) those who satisfied DEFUSE-3 or DAWN criteria (DOD). We used logistic regression to examine the impact of trial eligibility on two safety outcomes (symptomatic intracranial hemorrhage [sICH] and all-cause mortality at 3 months) and two efficacy outcomes (modified Rankin Score [mRS] shift toward lower categories and mRS of 0-2 at 3 months)., Results: Of 174 patients who received MT, 102 (59%) belonged to the NDND group. Rates of sICH were similar between the NDND group and the DOD group (3% vs. 4%, p  =  1.00). Multivariable regression revealed no differences in 3-month all-cause mortality (aOR 2.07, 95% CI 0.64-6.84, p  = 0.23) or functional outcomes (mRS shift: acOR 0.81, 95% CI 0.37-1.79, p  = 0.60; mRS 0-2: aOR 0.91, 95% CI 0.31-2.57, p  = 0.85 )., Conclusion: Among adult patients with LVO treated with MT between 6 and 24 h, safety and efficacy outcomes were similar between DEFUSE-3/DAWN eligible and ineligible patients. Our data provide a compelling rationale for randomized trials with broader inclusion criteria for MT.

Background: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear., Methods: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days., Results: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days., Conclusions: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.)., (Copyright © 2023 Massachusetts Medical Society.)