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Cervical artery dissection (CAD) is a rare cause of acute ischemic stroke (AIS) with large vessel occlusion (LVO) and may constitute a challenge for mechanical thrombectomy (MT). We compared procedural characteristics, reperfusion rates, and clinical outcome in AIS patients undergoing MT with and without CAD. We performed a pre-specified analysis of patients registered within the German Stroke Registry, a prospectively maintained multicenter registry of consecutive patients with AIS patients treated by MT. Procedural characteristics included time periods and additional application of medication. Of 2589 patients, 62 (2.4%) were diagnosed with CAD. CAD patients were younger, had lower rates of known vascular risk factors and larger baseline stroke volumes. MT in CAD patients took significantly longer (median [IQR] groin-puncture-to-flow restoration time: 98 [67-136] versus 70 [45-100] minutes; p < 0.001) and more often required use of intra-arterial medication (34.4% versus 15.6%; p < 0.001). Reperfusion success (modified Treatment in Cerebral Infarction score 2b-3: 85.2% versus 83.3%, p = 0.690) and favorable functional outcome after 3 months (modified Rankin Scale score ≤ 2: 70.9% versus 36.4%, adjusted p = 0.086) did not differ significantly between patients with and without CAD. The latter findings held true for both CAD in the anterior and posterior circulation. CAD in AIS requiring MT is rare. MT in patients with CAD constitutes a particular procedural challenge, but still achieves favorable radiological and functional outcomes in most patients. Our data provide indirect evidence that MT is of clinical benefit in patients with AIS due to LVO and CAD.

IntroductionFollowing a cerebrovascular event, the associated risks for further major adverse cerebro- and cardiovascular events and death (MACE) and important aspects of cognitive, mental and patient-reported outcomes are currently not understood, particularly long-term. Here, we present the study design of the ongoing Berlin Long-term Observation of Vascular Events (BeLOVE) stroke stratum and report data of the first study phase.Methods and analysisBeLOVE is a prospective, longitudinal, observational, hospital-based cohort study. Its stroke stratum enrols adult patients with acute ischaemic stroke, transient ischaemic attack (TIA) or non-traumatic intracerebral haemorrhage. Patients undergo deep phenotyping including cerebral and cardiac MRI, ECG, echocardiography and bio-sampling including multi-omics analyses. Regular, standardised follow-ups take place annually over a period of up to 10 years and record the frequency of MACE as the primary outcome.Secondary outcomes include the frequency, progression and interactions of functional impairments, namely post-stroke cognition, pain, depression, seizures and their relationship to quality of life.The first study phase included 758 patients (median 69 years, 37% female). At 2-year follow-up, the cumulative incidence (95% CI) of the composite primary endpoint MACE was 0.107 (0.085 to 0.132) and that of first ischaemic stroke, first myocardial infarction and death were 0.066 (0.049 to 0.086), 0.015 (0.008 to 0.026) and 0.040 (0.027 to 0.056), respectively.Ethics and disseminationEach participant will provide informed written consent during the acute in-hospital phase. Data will be available for research purposes via a written request to the data use and access committee.Trial registration numberGerman Clinical Trials Register: http://www.drks.de/DRKS00023323 on 4 November 2020.

IntroductionCardiac troponin (hs-cTnT) is a sensitive marker of myocardial injury and has been linked to incident dementia. The underlying mechanism of that observation is still unknown. Given that severity of cerebral small vessel disease is a predictor of cognitive decline, we aimed to explore whether there is an association between hs-cTnT and severity of white matter lesions (WML) as a marker of cerebral small vessel disease in patients with ischemic stroke.MethodsWe analyzed consecutive acute ischemic stroke patients admitted to Charité-University Hospital, Berlin from 2011 to 2013. Severity of WML was graded on 3T-MRI using the age-related white matter severity score (ARWMS). Patients with hs-cTnT elevation suggestive of acute coronary syndrome (ACS) were excluded (hs-cTnT > 52 ng/l or dynamic change of hs-cTnT > 50%, ESC guideline). We performed unadjusted and adjusted quantile regression models to assess the association between increased hs-cTnT (dichotomized at the 99th percentile, 14 ng/l) and severity of WML.ResultsA total of 860 patients was analyzed (median age 73 years, 44.8% female, median ARWMS 6). Patients with elevated hs-cTnT had more extensive WML than those without (median ARWMS 8 vs. 5, adjusted beta for 50th percentile 1.12, 95% CI 0.41–1.84). The association between WML and hs-cTnT elevation was strongest in patients with severe WML (adjusted beta 1.77, 95% CI 0.26–3.27 for 80th WML percentile).ConclusionElevated hs-cTnT levels were associated with extent of WML in acute stroke patients. Further studies are needed to assess whether hs-cTnT can be used to identify stroke patients at risk for cognitive decline.

BackgroundOcclusion 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.ObjectiveTo characterize EVT-treated patients with ICA-I- and ICA-E occlusion by comparing them with ICA-T occlusions.MethodsThe 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.ResultsOf 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)).ConclusionPatient 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.

Background Infective endocarditis (IE) is a rare yet challenging cause of acute stroke. A stroke imaging pattern with ischemic lesions in all three major cerebral vascular supply territories (three-territory sign), is considered typical for IE. However, data on its frequency and significance are scarce. Methods Data on IE patients with concomitant acute stroke admitted to three tertiary care hospitals in Berlin, Germany, between 2017 and 2023 were retrospectively analyzed. Presence of the three-territory sign was evaluated on cerebral magnetic resonance imaging (cMRI). Presence and distribution of accompanying hemorrhagic stroke, cerebral microbleeds (CMB) and chronic infarcts were evaluated, too. Bivariate and multivariable logistic regression analyses were performed to identify variables associated with three-territory sign. Results We identified 135 patients with IE and acute stroke on cMRI (median age 67 years [56–76], 31.9% female). Three-territory sign was present in 86/135 patients (63.7%). Three-territory sign was independently associated with detection of Staphylococcus aureus [adjusted odds ratio (aOR) = 3.98 (95% CI 1.35–11.75)] and additional extracerebral arterial embolism [aOR = 4.78 (95% CI 1.77–12.91)] but not with presence or distribution of hemorrhagic stroke, CMB or chronic infarcts. In-hospital mortality was higher in IE patients with three-territory sign compared to those without (31.4% vs. 12.2%; p  = 0.01). Conclusions Three-territory sign is common but not obligatory in IE patients with acute ischemic stroke. cMRI will rather depict this stroke pattern in the more severely diseased IE patients as three-territory sign makes detection of a particularly virulent pathogen (Staphylococcus aureus) more likely and indicates higher severity of disease. Trial registration Not applicable.

Background Current guidelines recommend measurement of troponin in acute ischemic stroke (AIS) patients. In AIS patients, troponin elevation is associated with increased mortality and worse outcome. However, uncertainty remains regarding the underlying pathophysiology of troponin elevation after stroke, particularly regarding diagnostic and therapeutic consequences. Troponin elevation may be caused by coronary artery disease (CAD) and more precisely acute coronary syndrome (ACS). Both have a high prevalence in stroke patients and contribute to poor outcome. Therefore, better diagnostic algorithms are needed to identify those AIS patients likely to have ACS or other manifestations of CAD. Methods/design The primary goal of the “PRediction of Acute coronary syndrome in acute Ischemic StrokE” (PRAISE) study is to develop a diagnostic algorithm for prediction of ACS in AIS patients. The primary hypothesis will test whether dynamic high-sensitivity troponin levels determined by repeat measurements (i.e., “rise or fall-pattern”) indicate presence of ACS when compared to stable (chronic) troponin elevation. PRAISE is a prospective, multicenter, observational trial with central reading and predefined endpoints guided by a steering committee. Clinical symptoms, troponin levels as well as findings on electrocardiogram, echocardiogram, and coronary angiogram will be recorded and assessed by central academic core laboratories. Diagnosis of ACS will be made by an endpoint adjudication committee. Severe adverse events will be evaluated by a critical event committee. Safety will be judged by a data and safety monitoring board. Follow-up will be conducted at three and twelve months and will record new vascular events (i.e., stroke and myocardial infarction) as well as death, functional and cognitive status. According to sample size calculation, 251 patients have to be included. Discussion PRAISE will prospectively determine the frequency of ACS and characterize cardiac and coronary pathologies in a large, multicenter cohort of AIS patients with troponin elevation. The findings will elucidate the origin of troponin elevation, shed light on its impact on necessary diagnostic procedures and provide data on the safety and diagnostic yield of coronary angiography early after stroke. Thereby, PRAISE will help to refine algorithms and develop guidelines for the cardiac workup in AIS. Trial registration NCT03609385 registered 1st August 2018.

Background In the general population, cognitive impairment and dementia are more common in individuals with prior myocardial injury, defined as elevated levels of high-sensitive cardiac troponin (hs-cTn). In stroke patients, data on the link between myocardial injury and cognitive outcome are scarce. We aimed to analyze the association between the severity of myocardial injury (degree of hs-cTn elevation), presence of acute myocardial injury (dynamic change in elevated hs-cTn values > 20% in serial measurements) and cognitive performance over time after acute ischemic stroke. Methods This is a prespecified analysis of the prospective multicenter observational PRediction of Acute coronary syndrome in acute Ischemic StrokE (PRAISE) study. PRAISE included 254 patients with an acute ischemic stroke or transient ischemic attack (TIA) and myocardial injury in 26 centers in Germany. Patients underwent cognitive assessment at baseline and before hospital discharge using the Montreal Cognitive Assessment (MoCA) and at three and twelve months after the index event using the Telephone Interview for Cognitive Status (TICS). We used linear regression to analyze the associations between cognitive performance and (1) severity of myocardial injury and (2) presence of acute myocardial injury. The association between hs-cTn and TICS scores over time was examined using inverse probability weighted generalized linear models. Results Severity of myocardial Injury was associated with lower MoCA scores (adjusted beta − 2.6, 95% CI -4.0 - -1.2, p  < 0.001) and higher proportion of cognitive impairment (i.e. MoCA score < 26 points) (adjusted OR 2.9, 95%CI 1.3–6.7, p  = 0.012). Acute myocardial injury was associated with better cognitive performance (adjusted beta 1.8, 95% CI 0.4–3.1, p  = 0.011). We found no association between hs-cTn and cognitive decline over twelve months. Conclusions In patients with ischemic stroke, the severity of myocardial injury in general but not the presence of acute myocardial injury at time of stroke is associated with cognitive impairment. Trial registration Clinicaltrials.gov NCT03609385 https://clinicaltrials.gov/study/NCT03609385?term=NCT03609385&rank=1 Date of registration 6th July 2018.

BackgroundIn patients with acute ischaemic stroke (AIS) and concomitant non-ST-elevation acute coronary syndrome (NSTE-ACS), the role of intravenous thrombolysis (IVT) before percutaneous coronary intervention (PCI) is unclear.MethodsWe performed a subanalysis of the PRAISE (PRediction of Acute coronary syndrome in acute Ischemic StrokE) study, a multicentre, prospective observational study in 247 patients with AIS and elevated high-sensitivity cardiac troponin who underwent coronary angiography based on European Society of Cardiology guidelines. The impact of IVT prior to PCI on coronary artery flow (Thrombolysis in Myocardial Infarction (TIMI) score) and myocardial perfusion (TIMI myocardial perfusion score) was compared using Fisher’s exact test and logistic regression analysis, adjusting for time from stroke onset to PCI.ResultsAmong 71 patients with AIS undergoing PCI, those who received IVT prior to PCI for NSTE-ACS (33 women; median age 77 (66–82 IQR)) achieved a TIMI grade 3 flow more frequently than those undergoing direct PCI (97% vs 79%; p=0.04). Regression analysis indicated a trend toward improved coronary artery flow with IVT (adjusted OR 8.5, 95% CI 0.9 to 75.3; p=0.05). Myocardial perfusion did not differ between groups (p=0.06).ConclusionsThis subanalysis suggests that IVT before PCI may enhance coronary artery flow in selected patients with NSTE-ACS with AIS. The results of this exploratory subanalysis warrant further investigation, particularly in patients with delayed access to PCI.

Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines—based on available evidence from mostly observational studies—suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0–3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI −4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.

Background Post-stroke heart rate (HR) and heart rate variability (HRV) changes have been proposed as outcome predictors after stroke. We used data lake-enabled continuous electrocardiograms to assess post-stroke HR and HRV, and to determine the utility of HR and HRV to improve machine learning-based predictions of stroke outcome. Methods In this observational cohort study, we included stroke patients admitted to two stroke units in Berlin, Germany, between October 2020 and December 2021 with final diagnosis of acute ischemic stroke or acute intracranial hemorrhage and collected continuous ECG data through data warehousing. We created circadian profiles of several continuously recorded ECG parameters including HR and HRV parameters. The pre-defined primary outcome was short-term unfavorable functional outcome after stroke indicated through modified Rankin Scale (mRS) score of > 2. Results We included 625 stroke patients, 287 stroke patients remained after matching for age and National Institute of Health Stroke Scale (NIHSS; mean age 74.5 years, 45.6% female, 88.9% ischemic, median NIHSS 5). Both higher HR and nocturnal non-dipping of HR were associated with unfavorable functional outcome ( p  < 0.01). The examined HRV parameters were not associated with the outcome of interest. Nocturnal non-dipping of HR ranked highly in feature importance of various machine learning models. Conclusions Our data suggest that a lack of circadian HR modulation, specifically nocturnal non-dipping, is associated with short-term unfavorable functional outcome after stroke, and that including HR into machine learning-based prediction models may lead to improved stroke outcome prediction.