Corrigendum: Tandem occlusions involving the internal carotid and anterior cerebral arteries-A rare form of stroke: results from the multicenter EVATRISP collaboration study.

[This corrects the article DOI: 10.3389/fneur.2022.1024891.].

Role of Cardiac Biomarkers in Stroke and Cognitive Impairment.

This topical review assesses the growing role of cardiac biomarkers beyond cardiovascular health and focuses on their importance in stroke and dementia. The first part describes blood-based cardiac biomarkers in patients with stroke and highlights applications in the setting of early diagnosis, poststroke complications, outcome prediction as well as secondary prevention. Among other applications, natriuretic peptides can be helpful in differentiating stroke subtypes. They are also currently being investigated to guide prolonged ECG monitoring and secondary prevention in patients with stroke. Elevated cardiac troponin after ischemic stroke can provide information about various poststroke complications recently termed the stroke-heart syndrome. The second part focuses on the role of cardiac biomarkers in vascular cognitive impairment and dementia, emphasizing their association with structural brain lesions. These lesions such as silent brain infarcts and white matter hyperintensities often co-occur with cardiac disease and may be important mediators between cardiovascular disease and subsequent cognitive decline. ECG and echocardiogram measurements, in addition to blood-based biomarkers, show consistent associations with vascular brain changes and incident dementia, suggesting a role in indicating risk for cognitive decline. Together, the current evidence suggests that cardiac blood-based, electrophysiological, and imaging biomarkers can be used to better understand the heart and brain connection in the setting of not only stroke but also dementia.

Fronto-thalamic networks and the left ventral thalamic nuclei play a key role in aphasia after thalamic stroke.

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca's area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca's area, during language processing.

Type 1 Myocardial Infarction in Patients With Acute Ischemic Stroke.

Importance: Elevated values of high-sensitivity cardiac troponin (hs-cTn) are common in patients with acute ischemic stroke and are associated with poor prognosis. However, diagnostic and therapeutic implications in patients with ischemic stroke remain unclear. Objective: To identify factors indicative of myocardial infarction (MI) in patients with acute ischemic stroke and hs-cTn elevation. The primary hypothesis was that a dynamic change of hs-cTn values (>50% change) in patients with acute ischemic stroke indicates MI. Design, Setting, and Participants: This cross-sectional study was a prospective, observational study with blinded end-point assessment conducted across 26 sites in Germany. Patients were included if they had acute ischemic stroke within 72 hours and either (1) highly elevated hs-cTn values on admission (>52 ng/L) or (2) hs-cTn levels above the upper limit of normal and a greater than 20% change at repeated measurements. Patients were enrolled between August 2018 and October 2020 and had 1 year of follow-up. Statistical analysis was performed between April 2022 and August 2023. Exposure: Standardized electrocardiography, echocardiography, and coronary angiography. Main Outcome and Measures: Diagnosis of MI as adjudicated by an independent end-point committee based on the findings of electrocardiography, echocardiography, and coronary angiography. Results: In total, 254 patients were included. End points were adjudicated in 247 patients (median [IQR] age, 75 [66-82] years; 117 were female [47%] and 130 male [53%]). MI was present in 126 of 247 patients (51%) and classified as type 1 MI in 50 patients (20%). Dynamic change in hs-cTn value was not associated with MI in univariable (32% vs 38%; χ2 P = .30) or adjusted comparison (odds ratio, 1.05; 95% CI, 0.31-3.33). The baseline absolute hs-cTn value was independently associated with type 1 MI. The best cutoffs for predicting type 1 MI were at hs-cTn values 5 to 10 times the upper limit normal. Conclusions and Relevance: This study found that in patients with acute ischemic stroke, a dynamic change in hs-cTn values did not identify MI, underscoring that dynamic changes do not identify the underlying pathophysiological mechanism. In exploratory analyses, very high absolute hs-cTn values were associated with a diagnosis of type 1 MI. Further studies are needed how to best identify patients with stroke who should undergo coronary angiography.

Aspiration only versus stent retriever only thrombectomy in basilar artery occlusion: a propensity score-matched analysis of the German Stroke Registry.

BACKGROUND: Endovascular treatment has become the standard care for acute basilar artery occlusion (BAO). Uncertainty persists about the optimal thrombectomy technique. OBJECTIVE: To compare aspiration thrombectomy with stent retriever thrombectomy in patients with BAO in a multicenter real-world patient population. METHODS: We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET). Patients with isolated BAO who underwent either aspiration or stent retriever thrombectomy were compared, including propensity score matching (PSM). The primary outcome measure was the modified Rankin Scale shift analysis at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), procedure complications, and metrics. RESULTS: Of 13 082 patients in the GSR-ET, 387 patients (mean age 72.0±13.1 years; 45.0% female) fulfilled the inclusion criteria. The thrombectomy technique was aspiration only in 195 (50.4%) and stent retriever only in 192 (49.6%) patients. Functional outcome did not differ between the groups, either before (common OR (cOR) 0.94; 95% CI 0.64 to 1.38) or after PSM (cOR=1.37; 95% CI 0.90 to 2.09). There was no significant difference in sICH (2.6 vs 5.5%; P=0.231; OR=0.46; 95% CI 0.14 to 1.47), but aspiration thrombectomy demonstrated fewer procedure-related complications (4.6% vs 12.5%; P=0.017), a shorter procedure duration (24 vs 48 min; P<0.001), and higher first pass recanalization rates (75.1% vs 44.8%; P<0.001). CONCLUSIONS: In this study both aspiration and stent retriever thrombectomy showed equal efficacy in terms of functional outcome in patients with BAO. However, procedure complications and metrics might favor aspiration over stent retriever thrombectomy.

Antithrombotic Treatment for Cervical Artery Dissection: A Systematic Review and Individual Patient Data Meta-Analysis.

Importance: Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. Objective: To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. Data Sources: PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023. Study Selection: Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. Data Extraction/Synthesis: Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator. Main Outcomes and Measures: The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses. Results: Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0). Conclusions and Relevance: This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.

High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

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.

Sex Differences in Outcomes of Acute Myocardial Injury After Stroke.

BACKGROUND: Sex differences in presentation, treatment, and prognosis of cardiovascular disorders are well recognized. Although an association between acute myocardial injury and mortality after ischemic stroke has been demonstrated, it is unclear whether prevalence and outcome of poststroke acute myocardial injury differ between women and men. METHODS AND RESULTS: We prospectively screened consecutive patients with acute ischemic stroke and serial high-sensitivity cardiac troponin T measurements admitted to our center. Acute myocardial injury was defined as at least 1 high-sensitivity cardiac troponin T value above the upper reference limit (14 ng/L) with a rise/fall of >20%. Rates of acute myocardial injury were also calculated using sex-specific high-sensitivity cardiac troponin T cutoffs (women upper reference limit, 9 ng/L; men upper reference limit, 16 ng/L). Logistic regression analyses were performed to evaluate the association between acute myocardial injury and outcomes. Of 1067 patients included, 494 were women (46%). Women were older, had a higher rate of known atrial fibrillation, were more likely to be functionally dependent before admission, had higher stroke severity, and more often had cardioembolic strokes (all P values <0.05). The crude prevalence of acute myocardial injury differed by sex (29% women versus 23% men, P=0.024). Statistically significant associations between acute myocardial injury and outcomes were observed in women (7-day in-hospital mortality: adjusted odds ratio [aOR], 3.2 [95% CI, 1.07-9.3]; in-hospital mortality: aOR, 3.3 [95% CI, 1.4-7.6]; modified Rankin Scale score at discharge: aOR, 1.6 [95% CI, 1.1-2.4]) but not in men. The implementation of sex-specific cutoffs did not increase the prognostic value of acute myocardial injury for unfavorable outcomes. CONCLUSIONS: The prevalence of acute myocardial injury after ischemic stroke and its association with mortality and greater disability might be sex-dependent. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892226.

Machine learning using multimodal and autonomic nervous system parameters predicts clinically apparent stroke-associated pneumonia in a development and testing study.

BACKGROUND: Stroke-associated pneumonia (SAP) is a preventable determinant for poor outcome after stroke. Machine learning (ML) using large-scale clinical data warehouses may be able to predict SAP and identify patients for targeted interventions. The aim of this study was to develop a prediction model for identifying clinically apparent SAP using automated ML. METHODS: The ML model used clinical and laboratory parameters along with heart rate (HR), heart rate variability (HRV), and blood pressure (BP) values obtained during the first 48 h after stroke unit admission. A logistic regression classifier was developed and internally validated with a nested-cross-validation (nCV) approach. For every shuffle, the model was first trained and validated with a fixed threshold for 0.9 sensitivity, then finally tested on the out-of-sample data and benchmarked against a widely validated clinical score (A2DS2). RESULTS: We identified 2390 eligible patients admitted to two-stroke units at Charité between October 2020 and June 2023, of whom 1755 had all parameters available. SAP was diagnosed in 96/1755 (5.5%). Circadian profiles in HR, HRV, and BP metrics during the first 48 h after admission exhibited distinct differences between patients with SAP diagnosis vs. those without. CRP, mRS at admission, leukocyte count, high-frequency power in HRV, stroke severity at admission, sex, and diastolic BP were identified as the most informative ML features. We obtained an AUC of 0.91 (CI 0.88-0.95) for the ML model on the out-of-sample data in comparison to an AUC of 0.84 (CI 0.76-0.91) for the previously established A2DS2 score (p < 0.001). The ML model provided a sensitivity of 0.87 (CI 0.75-0.97) with a corresponding specificity of 0.82 (CI 0.78-0.85) which outperformed the A2DS2 score for multiple cutoffs. CONCLUSIONS: Automated, data warehouse-based prediction of clinically apparent SAP in the stroke unit setting is feasible, benefits from the inclusion of vital signs, and could be useful for identifying high-risk patients or prophylactic pneumonia management in clinical routine.

Heart rate turbulence in acute ischemic stroke.

BACKGROUND: Heart rate turbulence (HRT), an ECG-based marker of autonomic cardiac regulation, has shown high prognostic value in patients with established cardiovascular diseases, while data in patients with acute ischemic stroke are scarce. PATIENTS AND METHODS: The HRT parameters turbulence onset and turbulence slope were analyzed using Holter-ECG recordings from patients with acute ischemic stroke, consecutively enrolled in the prospective observational HEBRAS study. HRT was categorized as normal (category 0; both parameters normal), abnormal (category 1; one parameter abnormal), or severely abnormal (category 2; both parameters abnormal). Outcomes of interest were functional outcome according to modified Rankin Scale (mRS) score at 3 months, mortality at 1 year, newly detected atrial fibrillation (AF), and evidence of focal myocardial fibrosis on cardiovascular MRI. RESULTS: HRT was assessed in 335 patients in sinus rhythm (median age 69 years, 37% female, median NIHSS score 2 on admission), including 262 (78%) with normal HRT, 47 (14%) with abnormal and 26 (8%) with severely abnormal HRT. Compared with normal HRT, severely abnormal HRT was associated with increased disability [higher mRS] at 3 months (adjusted odds ratio [aOR]: 2.9, 95% confidence interval [CI]: 1.3-6.6), new AF (aOR: 3.5, 95% CI: 1.1-10.6), MRI-detected myocardial fibrosis (aOR: 5.8, 95% CI: 1.3-25.9), but not with mortality at 1 year after stroke (aOR: 3.0, 95% CI: 0.7-13.9). Abnormal HRT was not associated with the analyzed outcomes. CONCLUSIONS: Severely abnormal HRT was associated with increased disability and previously unknown cardiac comorbidities. The potential role of HRT in selecting patients for extended AF monitoring and cardiac imaging should be further investigated.

Protocol of the Berlin Long-term Observation of Vascular Events (BeLOVE): a prospective cohort study with deep phenotyping and long-term follow up of cardiovascular high-risk patients.

INTRODUCTION: The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations. METHODS AND ANALYSIS: A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes. ETHICS AND DISSEMINATION: The study was approved by the Charité-Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations. STUDY REGISTRATION: First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021.

Datawarehouse-enabled quality control of atrial fibrillation detection in the stroke unit setting.

Objective: (1) To assess the accuracy of a standard operating procedure (SOP) regarding the utilization of atrial fibrillation (AF) alarms in everyday clinical practice, and (2) to evaluate the performance of automated continuous surveillance for atrial fibrillation (AF) in hospitalized acute stroke patients. Design: Retrospective cohort study. Setting: Two stroke units from two tertiary care hospitals in Berlin, Germany. Participants: We identified 635 patients with ischemic stroke diagnosis for the time period between 01. January and 30. September 2021 of which 176 patients had recorded AF alarms during monitoring. Of those, 115 patients were randomly selected for evaluation. After excluding 6 patients with hemorrhagic stroke in their records, 109 patients (mean age: 79.1 years, median NIHSS at admission: 6, 57% female) remained for analysis. Intervention: Using a clinical data warehouse for comprehensive data storage we retrospectively downloaded and visualized ECG data segments of 65 s duration around the automated AF alarms. We restricted the maximum number of ECG segments to ten per patient. Each ECG segment plot was uploaded into a REDCap database and categorized as either AF, non-AF or artifact by manual review. Atrial flutter was subsumed as AF. These classifications were then matched with 1) medical history and known diseases before stroke, 2) discharge diagnosis, and 3) recommended treatment plan in the medical history using electronic health records. Main outcome measures: The primary outcome was the proportion of previously unknown AF diagnoses correctly identified by the monitoring system but missed by the clinical team during hospitalization. Secondary outcomes included the proportion of patients in whom a diagnosis of AF would likely have led to anticoagulant therapy. We also evaluated the accuracy of the automated detection system in terms of its positive predictive value (PPV). Results: We evaluated a total of 717 ECG alarm segments from 109 patients. In 4 patients (3.7, 95% confidence interval [CI] 1.18-9.68%) physicians had missed AF despite at least one true positive alarm. All four patients did not receive long-term secondary prevention in form of anticoagulant therapy. 427 out of 717 alarms were rated true positives, resulting in a positive predictive value of 0.6 (CI 0.56-0.63) in this cohort. Conclusion: By connecting a data warehouse, electronic health records and a REDCap survey tool, we introduce a path to assess the monitoring quality of AF in acute stroke patients. We find that implemented standards of procedure to detect AF during stroke unit care are effective but leave room for improvement. Such data warehouse-based concepts may help to adjust internal processes or identify targets of further investigations.

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

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

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

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

Endovascular therapy in patients with internal carotid artery occlusion and patent circle of Willis.

BACKGROUND: Occlusion of the internal carotid artery (ICA) may extend into the middle or anterior cerebral artery (ICA-T) or be confined to the intracranial (ICA-I) or extracranial segment (ICA-E). While there is excellent evidence for endovascular therapy (EVT) in ICA-T occlusions, studies on EVT in non-tandem ICA-I or ICA-E occlusions are scarce. OBJECTIVE: To characterize EVT-treated patients with ICA-I- and ICA-E occlusion by comparing them with ICA-T occlusions. METHODS: The German Stroke Registry (GSR), a national, multicenter, prospective registry was searched for EVT-treated patients with isolated ICA occlusion between June 2015 and December 2021. We stratified patients by ICA occlusion site: (a) ICA-T, (b) ICA-I, (c) ICA-E. Baseline factors, procedural variables, technical (modified Thrombolysis in Cerebral Infarction (mTICI)), and functional outcomes (modified Rankin scale score at 3 months) were analyzed. RESULTS: Of 13 082 GSR patients, 2588 (19.8%) presented with an isolated ICA occlusion, thereof 1946 (75.2%) ICA-T, 366 (14.1%) ICA-I, and 276 (10.7%) ICA-E patients. The groups differed in age (77 vs 76 vs 74 years, Ptrend=0.02), sex (53.4 vs 48.9 vs 43.1% female, Ptrend<0.01), and stroke severity (median National Institutes of Health Stroke Scale score at admission 17 vs 14 vs 13 points, Ptrend<0.001). In comparison with ICA-T occlusions, both ICA-I and ICA-E occlusions had lower rates of successful recanalization (mTICI 2b/3: 85.4% vs 80.4% vs 76.3%; aOR (95% CI for ICA-I vs ICA-T 0.71 (0.53 to 0.95); aOR (95% CI) for ICA-E vs ICA-T 0.57 (0.42 to 0.78)). In adjusted analyses, ICA-E occlusion was associated with worse outcome when compared with ICA-T occlusion (mRS ordinal shift, cOR (95% CI) 0.70 (0.52 to 0.93)). CONCLUSION: Patient characteristics and outcomes differ substantially between ICA-T, ICA-I, and ICA-E occlusions. These results warrant further studies on EVT in ICA-I and ICA-E patients.

Incidence and outcome of perforations during medium vessel occlusion compared with large vessel occlusion thrombectomy.

BACKGROUND: Vessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation. METHODS: In this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0-2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t-test for unpaired samples were used for statistical analysis. RESULTS: During 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p<0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p=0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation. CONCLUSIONS: In our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures.

Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration.

BACKGROUND AND PURPOSE: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD). METHODS: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015-2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0-2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching. RESULTS: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10-19] vs. 4 [2-7], P<0.001). The frequency of favorable 3-month outcome did not differ significantly between both groups (EVT: 64.0% vs. IVT: 86.8%; ORadjusted 0.56 [0.24-1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28-18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group. CONCLUSION: We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research.

Enhanced diagnostic workup increases pathological findings in patients with acute ischaemic stroke: results of the prospective HEBRAS study.

BACKGROUND: Stroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke (AIS). We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care in-hospital. METHODS: Hospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke (HEBRAS) study at the Charité, Berlin, Germany. Patients with AIS without known atrial fibrillation (AF) underwent cardiovascular MR imaging (CMR), MR-angiography of the aortic arch and prolonged Holter-ECG monitoring on top of routine diagnostic care. RESULTS: Among 356 patients with AIS (mean age 66 years, 37.6% female), enhanced workup yielded a higher rate of prespecified pathological findings compared with routine care (17.7% vs 5.3%; p<0.001). Consequently, fewer patients were classified as cryptogenic after enhanced diagnostic workup (38.5% vs 45.5%, p<0.001). Routine care included echocardiography in 228 (64.0%) patients. CMR was successfully performed in 292 (82.0%) patients and revealed more often a prespecified pathological finding compared with routine echocardiography (16.1% vs 5.3%). Furthermore, study-related ECG monitoring (median duration 162 hours (IQR 98-210)) detected AF in 16 (4.5%) patients, while routine monitoring (median duration 51 hours (IQR 34-74)) detected AF in seven (2.0%) patients. CONCLUSIONS: Enhanced diagnostic workup revealed a higher rate of prespecified pathological findings in patients with AIS compared with routine diagnostic care and significantly reduced the proportion of patients with cryptogenic stroke. TRIAL REGISTRATION NUMBER: NCT02142413.