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Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Background and Purpose— Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods— Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results— A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care ( P =0.002). Median BNP was higher in patients with pAF as compared to patients without AF in both study arms at baseline (57.8 versus 28.3 pg/mL in the EPM arm, P =0.0003; 46.2 versus 27.7 pg/mL, P =0.28 in the control arm) and after 3 months (74.9 versus 31.3 pg/mL, P =0.012 in the EPM arm, 99.3 versus 26.3 pg/mL, P =0.02 in the control arm). Applying a cut off of 100 pg/mL, the number needed to screen was reduced from 18 by usual care to 3 by EPM. Conclusions— BNP measured early after ischemic stroke identifies a subgroup of patients with stroke at increased risk for AF, in whom EPM is particularly efficacious. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01855035.

Background and Purpose— Ischemic stroke causes major disability as a consequence of neuronal loss and recurrent ischemic events. Biomarkers predicting tissue damage or stroke recurrence might be useful to guide an individualized stroke therapy. NfL (neurofilament light chain) is a promising biomarker that might be used for this purpose. Methods— We used individual data of patients with an acute ischemic stroke and clinical long term follow-up. Serum NfL (sNfL) was quantified within 24 hours after admission and after 1 year and compared with other biomarkers (GDF15 [growth differentiation factor 15], S100, NT-proBNP [N-terminal pro-B-type natriuretic peptide], ANP [atrial natriuretic peptide], and FABP [fatty acid–binding protein]). The primary end point was functional outcome after 90 days and cerebrovascular events and death (combined cardiovascular end point) within 36 months of follow-up. Results— Two hundred eleven patients (mean age, 68.7 years; SD, ±12.6; 41.2% women) with median clinical severity on the National Institutes of Health Stroke Scale (NIHSS) score of 3 (interquartile range, 1–5) and long-term follow-up with a median of 41.8 months (interquartile range, 40.0–44.5) were prospectively included. We observed a significant correlation between sNfL and NIHSS at hospital admission (r=0.234; P P P =0.048) together with NIHSS (OR, 1.303; 95% CI, 1.164–1.458; P P =0.022). Similarly, sNfL was valuable for the prediction of the combined cardiovascular end point (OR, 2.002; 95% CI, 1.213–3.302; P =0.007), besides NIHSS (OR, 1.110; 95% CI, 1.000–1.232; P =0.049), diabetes mellitus (OR, 2.942; 95% CI, 1.306–6.630; P =0.005), and age-related white matter change rating (severe; OR, 4.816; 95% CI, 1.206–19.229; P =0.026) after multivariate regression analysis. Kaplan-Meier analysis revealed significantly more combined cardiovascular end points (18 [14.1%] versus 38 [45.8%], log-rank test P Conclusions— sNFL is a valuable biomarker for functional independence 90 days after ischemic stroke and predicts cardiovascular long-term outcome. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN 46104198.

Background and Purpose Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk.Methods We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months.Results Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37).Conclusions Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

Objective:Prolonged ECG monitoring after stroke frequently reveals short paroxysmal atrial fibrillation (pAF) and supraventricular (SV) runs. The minimal duration of atrial fibrillation (AF) required to induce cardioembolism, the relevance of SV runs, and whether short pAF results from cerebral damage itself are currently being debated. We aimed to study the relevance of SV runs and short pAF detected by prolonged Holter ECG after cerebral ischemia during long-term follow-up.Methods:Analysis is from the prospective Find-AF trial (ISRCTN46104198). We included patients with acute cerebral ischemia. Those without AF on admission received 7-day Holter ECG monitoring. We differentiated patients with AF on admission (AF-adm), with pAF (>30 seconds), with SV runs (>5 beats but Results:A total of 254 of 281 initially included patients were analyzed (mean age 70.0 years, 45.3% female). Forty-three (16.9%) had AF-adm. A total of 211 received 7-day Holter ECG monitoring: 27 (12.8%) had pAF, 67 (31.8%) had SV runs, and 117 (55.5%) were controls. During a mean 3.7 years of follow-up, the SV runs group had more recurrent strokes (p = 0.04) and showed numerically more novel AF (12% vs 5%, p = 0.09) than the controls. Seventy-five percent of the patients with manifest pAF detected after cerebral ischemia still had AF during follow-up (50% paroxysmal, 50% persisting/permanent).Conclusions:Patients with cerebral ischemia and SV runs had more recurrent strokes and numerically more novel AF during follow-up and could benefit from further prolonged ECG monitoring. pAF detected after stroke is not a temporal phenomenon.

Background and Purpose- Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods- Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results- A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care (

Background: The cardiac diagnostic workup of stroke patients, especially the value of echocardiography and prolonged and enhanced Holter-ECG monitoring (EPM), is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis. Methods: Find-AF RANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to EPM or usual stroke unit care. Therapeutic consequences of echocardiography and routine Holter-ECG or EPM, respectively, were compared and one-year mortality was calculated. Results: 50.3% received EPM and 49.7% routine ECG monitoring. 82.9 % underwent transthoracic echocardiography (TTE), 38.9 % transesophageal echocardiography (TEE) and 25.6 % both procedures. 14/90 TEE pathologies and 1/89 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 334, respectively. In comparison, EPM found atrial fibrillation (AF) in 27 of 200 patients, and routine ECG monitoring in twelve of 198 patients, leading to therapeutic changes in all patients (NNCD 8 and 17, respectively). We found a trend towards a higher one-year mortality in patients with pathologic echocardiographic findings (p = 0.093). Conclusions: Most changes in therapeutic decisions were caused by EPM, which should therefore play a more prominent role in future guidelines. Echocardiography identifies a patient group at high cardiovascular risk, but rarely result in therapeutic changes. Whether this patient group requires further cardiovascular workup remains unknown. This should be further investigated by interdisciplinary neurocardiologic teams and in appropriate future trials.

Background: Detecting concealed paroxysmal atrial fibrillation (pAF) is a major focus of the workup of ischemic-stroke-patients, but requires elaborate ECG-monitoring. We aimed to evaluate pre-specified predictors to determine stroke patients with an increased probability of underlying pAF. We applied cut-off-levels recently suggested by the German Stroke Society 1 . Methods: The Find-AF RANDOMISED -trial (NCT01855035) evaluated 3x10-day Holter-ECG vs. standard-care in 398 patients > 60 years with acute ischemic strokes. The primary endpoint was novel pAF after 6 months. 27 patients in the intervention arm (13.5 %) and 9 patients in the control arm (9.0 %) met the primary endpoint (p=0.002). We used Pearson’s Chi 2 -test and the Mann-Whitney-U-test, as applicable. In variables with p Results: Table 1 shows known pAF-risk-factors in relation to whether patients had pAF. The absence of a clinical lacunar syndrome (p=0.007) or lacunar lesions (p=0.018), increased NIHSS-Score (p=0.003), frequent atrial premature beats (APB, p=0.003), prolonged supraventricular runs (p=0.01), enlarged left atria (p=0.07) and increased brain-natriuretic-peptide-levels (p=0.001) were associated with underlying pAF. Frequent APB differentiated best between those with and without pAF (area under the curve, AUC: 0.71). Conclusions: Several of the evaluated markers are useful to preselect stroke patients for enhanced ECG-monitoring. APB and comprehensive measures of both left atrial size and function (LAVI/a’) showed the highest AUC and should be used when preselecting stroke patients for prolonged ECG-monitoring.

Background Although endovascular treatment for proximal cerebral vessel occlusion is very effective, it remains controversial if intravenous thrombolysis (IVT) prior to endovascular treatment is superior compared to endovascular treatment alone. In this study we compared functional outcomes and recanalization rates of endovascularly treated stroke patients with and without bridging IVT. Methods Patients with acute large artery occlusion within the anterior and posterior cerebral circulation eligible for intraarterial revascularization with and without prior IVT were included in this monocentric, prospective observational study. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) were determined at baseline, discharge and 90-days follow up after stroke. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3. Results Of the 109 patients included, 81 (74%) received bridging therapy with i.v.-rtPA prior to endovascular treatment, 28 (26%) received endovascular treatment alone. There was no difference in groin-to-reperfusion time between the groups (54 vs 50 min; p = 0.657), but a trend towards a higher reperfusion rate in patients with bridging therapy (69 vs 15 patients, p = 0.099). Mean improvement of the NIHSS during hospitalization was 8 points (SD; ± 8) in the bridging-group and 2 points (SD, ± 7) in the non-bridging-group (p = 0.001). Number of patients with discharge mRS 0–2 (34 vs 5; p = 0.024) and 90-days mRS 0–2 (35 vs 6; p = 0.061) was higher in the bridging-group compared to the non-bridging-group. Conclusions This study provides evidence that bridging therapy with i.v.-rtPA improves functional outcome in patients eligible for endovascular treatment. Further studies are needed to confirm our findings and to identify patients most likely benefitting from bridging therapy.

BACKGROUND AND PURPOSE Endovascular therapy (ET) is superior to intravenous thrombolysis (IVT) in selected patients with anterior circulation large vessel occlusions. However, it is unclear if this positive effect also applies to patients with extensive early ischaemic changes. The aim of this study was to analyze the impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on the CT angiography source images (SI) on outcome after ET or IVT. METHODS Using our prospectively obtained stroke database and the admission SI-ASPECTS divided into three groups (0-5, 6-7 and 8-10), primarily the rates of good outcome [modified Rankin Scale (mRS) ≤2 at discharge] after either ET (n = 255) or IVT (n = 479) were compared. RESULTS A favorable SI-ASPECTS (8-10) was present in 501 patients, 132 patients had a moderately favorable SI-ASPECTS (6-7) and 101 patients had an unfavorable SI-ASPECTS (0-5). Irrespective of the treatment modality, no patient with an unfavorable SI-ASPECTS had a good outcome and 38% died during hospital stay. Whilst significantly more patients with a favorable SI-ASPECTS had a good outcome after ET than after IVT (51% vs. 35%, P < 0.01), there was only a non-significant trend towards a good outcome after ET than after IVT in patients with a moderately favorable ASPECTS (25% vs. 14%, P = 0.1). CONCLUSION Patients with extensive early ischaemic changes on CT scans (SI- ASPECTS ≤5) might not profit from ET. The impact of ET on outcome in patients with moderately favorable SI-ASPECTS should be addressed in further trials.

Background In patients with large vessel occlusions, endovascular treatment has been shown to be superior to intravenous thrombolysis in recent trials. Aims The aim of this study was to analyze the impact of endovascular treatment on clinical and radiological outcome in everyday clinical practice. Methods We compared the rates of good outcome (modified Rankin scale ≤ 2 at discharge), in-hospital death, symptomatic intracranial hemorrhages, and infarct sizes in patients with distal intracranial carotid artery, M1 and M2 occlusions during two time periods. Results From January 2008 to October 2012, a total of 509 patients were treated with intravenous thrombolysis and from November 2012 to December 2014, a total of 270 patients received endovascular treatment with stent retrievers (with or without intravenous thrombolysis). Significantly, more patients in the endovascular treatment group than in the intravenous thrombolysis group had a good outcome (37% vs. 27%, p Conclusion In everyday clinical practice and compared with intravenous thrombolysis, endovascular treatment significantly improved clinical outcome and was associated with smaller infarctions. This beneficial effect appeared to be highest in older patients, more severely affected patients, and in those with M1 occlusions.

Background and Purpose— Patient selection is crucial in the endovascular treatment of acute ischemic stroke patients. Baseline computed tomographic (CT) images, evaluated with the Alberta Stroke Program Early CT Scale (ASPECTS), are considered significant predictors of outcome. In this study, we evaluated CT images and perfusion parameters, analyzed with ASPECTS, as final outcome predictors after endovascular stroke treatment. Methods— We analyzed a cohort of patients with acute ischemic stroke and endovascular treatment. Patients with an occlusion of the M1 segment and multimodal CT imaging were included. CT perfusion data were reconstructed using commercial software. Two experienced neuroradiologists separately reviewed and scored CT and CT perfusion images with the ASPECTS score. Parameters were compared between patients with poor and with favorable follow-up outcome. Significantly different variables were further analyzed by forward stepwise logistic regression. Results— Fifty-one patients were included in our study. Baseline characteristics did not differ between patients with favorable and poor outcomes. No significant difference in recanalization status, the various times, or CT ASPECTS was demonstrated between these 2 groups. Significant differences were demonstrated for age ( P =0.0049), cerebral blood volume ASPECTS ( P =0.0007), and between cerebral blood volume and cerebral blood flow ASPECTS ( P =0.0045). Cerebral blood volume ASPECTS >7 demonstrated the highest sensitivity and specificity for favorable outcome with 84% and 79%, respectively. Conclusions— CT perfusion parameters, evaluated with ASPECTS, are optimal predictors of outcome and are more sensitive and specific than CT ASPECTS in the prediction of favorable outcome. Use of these parameters in treatment decisions could reduce futile recanalizations.

BACKGROUND AND PURPOSE: In patients with acute stroke, the location and extent of intravascular thrombi correlate with clinical and imaging outcomes and have been used to predict the success of intravenous thrombolysis. We hypothesized that 4D-CTA reconstructed from whole-brain CTP more closely outlines intracranial thrombi than conventional single-phase CTA. MATERIALS AND METHODS: Sixty-seven patients with anterior circulation occlusion were retrospectively analyzed. For 4D-CTA, temporal maximum intensity projections were calculated that combine all 30 spiral scans of the CTP examination through temporal fusion. Thrombus extent was assessed by a semi-quantitative clot burden score (0–10; in which 0 = complete unilateral anterior circulation occlusion and 10 = patent vasculature). In patients with sufficient collateral flow, the length of the filling defect and corresponding hyperdense middle cerebral artery sign on NCCT were measured. RESULTS: Clot burden on temporal maximum intensity projection (median clot burden score, 7.0; interquartile range, 5.1–8.0) was significantly lower than on single-phase CT angiography (median, 6.0; interquartile range, 4.5–7.0; P < .0001). The length of the hyperdense middle cerebral artery sign (14.30 ± 5.93 mm) showed excellent correlation with the filling defect in the middle cerebral artery on temporal maximum intensity projection (13.40 ± 6.40 mm); this filling defect was larger on single-phase CT angiography (18.08 ± 6.54 mm; P = .043). CONCLUSIONS: As the result of an increased sensitivity for collateral flow, 4D-CTA temporal maximum intensity projection more closely outlines intracranial thrombi than conventional single-phase CT angiography. Our findings can be helpful when planning acute neurointervention. Further research is necessary to validate our data and assess the use of 4D-CTA in predicting response to different recanalization strategies.

Flat-panel angiographic CT after intravenous contrast agent application (ivACT) is increasingly used as a follow-up examination after coiling, clipping, or stenting. The purpose of this study was to evaluate the feasibility of a new metal artefact reduction algorithm (MARA) in patients treated for intracranial aneurysms and stenosis.IvACT was performed on a flat-panel detector angiography system after intravenous application of 80 ml contrast media. The uncorrected raw images were transferred to a prototype reconstruction workstation where the MARA was applied. Two experienced neuroradiologists examined the corrected and uncorrected images on a commercially available workstation.Artefacts around the implants were detected in all 16 uncorrected cases, while eight cases showed remaining artefacts after correction with the MARA. In the cases without correction, there were 11 cases with "extensive" artefacts and five cases with "many" artefacts. After correction, seven cases showed "few" and only one case "many" artefacts (Wilcoxon test, P0.001). Parent vessels were characterized as "not identifiable" in 62% of uncorrected images, while the delineation of parent vessels were classified as "excellent" in 50% of the cases after correction (Wilcoxon test, P = 0.001).Use of the MARA in our study significantly reduced artefacts around metallic implants on ivACT images and allowed for the delineation of surrounding structures.

Background and purpose Clinical scores are recommended for predicting cardiovascular risk in patients with cerebral ischaemia to inform secondary prevention. Blood biomarkers may improve prediction beyond clinical scores. Methods Within the observational Find-AF trial (ISRCTN46104198), 197 patients >18 years of age with cerebral ischaemia and without atrial fibrillation had blood sampled at baseline. The predictive value of five biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to the Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2) and National Institutes of Health Stroke Scale (NIH-SS). Results There were 23 vascular events (11.7%) and 13 deaths (6.6%) to 1 year follow-up. In multivariate analyses of all markers, only high-sensitivity troponin T (hsTropT) remained independently predictive for vascular events (p=0.045) and all-cause mortality (p=0.004). hsTropT was higher in patients with a vascular event (median 12.7 ng/ml vs 5.1 ng/ml), and patients with hsTropT above the median of 6.15 ng/ml had vascular events more frequently (HR 3.86, p=0.008). For prediction of vascular events as well as all-cause mortality, hsTropT significantly improved multivariate Cox regression models with ESRS, SPI-2 or NIH-SS. The c-statistic increased non-significantly from 0.695 (ESRS) or 0.710 (hsTropT) to 0.747 (ESRS+hsTropT) and from 0.699 (SPI-2) to 0.763 (SPI-2+hsTropT). No patient with a low-risk ESRS and an hsTropT below the median had a vascular event or died. Conclusions hsTropT predicts vascular events and all-cause mortality in patients with acute cerebral ischaemia and improves prediction beyond established clinical scores.

Introduction: Undiagnosed atrial fibrillation (UAF) is a major burden in ischemic stroke. However, randomised trials have partly shown astonishingly low AF detection rates (e. g. in the CRYSTAL-AF study). This may be due to differences in baseline and stroke characteristics between studies. Hypothesis: We hypothesized that stroke patients in a randomised controlled trial have less severe strokes than patients in an observational trial with similar inclusion and exclusion criteria. Methods: We used data from the Find-AF observational (NCT 01855035) and the Find-AF randomised controlled trial (ISRCTN 46104198). We included only patients at study site Goettingen of the Find-AF randomised controlled trial (n=153) and only included patients from the Find-AF observational trial that fulfilled the inclusion/exclusion criteria of Find-AF randomised (n=90). We compared baseline characteristics of screened versus included patients in Find-AF randomised and baseline characteristics and stroke severity parameters between both studies. Data are shown as mean (Standard Deviation) or Median (25%; 75% percentile) and were compared by chi-square, t-test or Mann-Whitney U test. Results: Table 1 shows as comparison between baseline characteristics of both studies Comparing patients fulfilling the inclusion/exclusion criteria of Find-AF randomised, but unwilling to give informed consent to randomised patients showed a significant difference in age (77 ± 11 vs. 74 ± 8; p< 0.001), but no difference in gender (p=0.581). Conclusions: Both studies included patients similar in age, gender and many comorbidities. Major differences occurred in NIHSS and MRS. As NIHSS is a predictor of atrial fibrillation, randomized controlled trials investigating AF detection should include a minimum NIHSS to avoid a selection bias towards less severe strokes.

To assess the incidence and clinical significance as well as predictors of in-stent restenosis (ISR) after carotid artery stenting (CAS) diagnosed with serial duplex sonography investigations. We analyzed 215 CAS procedures that had clinical and serial carotid duplex ultrasound investigations. The incidence of in-stent restenosis (ISR) and periprocedural as well as long-term clinical complications were recorded. The influence of an ISR on clinical complication was analyzed using Kaplan-Meier curves and clinical risk factors for the development of an ISR with multivariate logistic regression. During a median follow-up time of 33.4 months (interquartile range 15.3–53.7) an ISR of ≥70% was detected in 12 (6.1%) of 215 arteries (mean age of 68.1 ± 9.8 years, 71.6% male). The combined stroke and death rate during long-term follow-up was significantly higher in the group with an ISR [odds ratio (OR): 3.59, 95% confidence interval (CI): 1.50–8.59, p = 0.004]. After applying multivariate logistic regression analysis contralateral carotid occlusion (OR 10.11, 95% CI 2.06–49.63, p = 0.004), carotid endarterectomy (CEA) restenosis (OR 8.87, 95% CI 1.68–46.84, p = 0.010) and postprocedural carotid duplex ultrasound with a PSV ≥120 cm/s (OR 6.33, 95% CI 1.27–31.44, p = 0.024) were independent predictors of ISR. ISR after CAS during long-term follow-up is associated with a higher proportion of clinical complications. A close follow-up is suggested especially in those patients with the aforementioned independent predictors of an ISR. Against the background of a lacking established treatment of ISR, these findings should be taken into account when offering CAS as a treatment alternative to CEA. peerReviewed

Treatment of a symptomatic stenosis is known to be most beneficial within 14 days after the presenting event but this can frequently not be achieved in daily practice. The aim of this study was the assessment of factors responsible for this time delay to treatment. A retrospective analysis of a prospective two-center CAS database was carried out to investigate the potential factors that influence a delayed CAS treatment. Of 374 patients with a symptomatic carotid stenosis, 59.1% were treated beyond ≥14 days. A retinal TIA event (OR = 3.59, 95% CI 1.47-8.74, p < 0.01) was found to be a predictor for a delayed treatment, whereas the year of the intervention (OR = 0.32, 95% CI 0.20-0.50, p < 0.01) and a contralateral carotid occlusion (OR = 0.42, 95% CI 0.21-0.86, p = 0.02) were predictive of an early treatment. Similarly, within the subgroup of patients with transient symptoms, the year of the intervention (OR = 0.28, 95% CI 0.14-0.59, p < 0.01) was associated with an early treatment, whereas a retinal TIA as the qualifying event (OR = 6.96, 95% CI 2.37-20.47, p < 0.01) was associated with a delayed treatment. Treatment delay was most pronounced in patients with an amaurosis fugax, whereas a contralateral carotid occlusion led to an early intervention. Although CAS is increasingly performed faster in the last years, there is still scope for an even more accelerated treatment strategy, which might prevent future recurrent strokes prior to treatment. peerReviewed

PurposeCarotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA) for patients with significant carotid stenosis. However, diffusion-weighted imaging (DWI) has indicated that CAS is associated with a significantly higher burden of microemboli. This study evaluated the potential effect on intellectual functions of new DWI lesions after CEA or CAS.MethodsThis prospective study analyzed the neuropsychologic outcomes after revascularization in 24 CAS and 31 CEA patients with severe carotid stenosis compared with a control group of 27 healthy individuals. All patients underwent clinical examinations, magnetic resonance imaging scans, and a neuropsychologic test battery that assessed six major cognitive domains performed immediately before CEA or CAS, ≤72 hours after, and at 3 months.ResultsNew DWI lesions were detected among 15 of 21 (71%) of the CAS patients immediately after treatment but in only 1 of the 28 CEA patients (4%; P < .01). As a group, patients with new DWI lesions showed a decline in their performance in the cognitive domains, attention, and visuoconstructive functions within 72 hours of carotid revascularization. Individually, however, in none of the cognitive domains did the decreases reach a clinically relevant threshold of z < −1.5. Moreover, the cognitive performance was not significantly different between patients with and without new DWI lesions 3 months after treatment. The cognitive performance was similar between CEA and CAS patients at all points.ConclusionsThe findings support the assumption that new brain lesions, as detected with DWI after CAS or CEA, do not affect cognitive performance in a manner that is long-lasting or clinically relevant. Despite the higher embolic load detected by DWI, CAS is not associated with a greater cognitive decline than CEA.

Background and purpose While carotid artery stenting can be performed safely in many patients, some have a higher risk for periprocedural complications. The detection of embolic lesions after CAS with DWI could become a useful means to identify these patients. The aim of this study was to determine risk factors for new DWI lesions after CAS. Methods One hundred seventy-six patients who had undergone protected CAS with pre- and postprocedural DWI between November 2000 and December 2006 were included in this retrospective investigation. The association of potential angiographic and clinical risk factors with the incidence of any new ipsilateral DWI lesion after CAS was analyzed with logistic regression analysis. Subsequently, a simple risk score was developed using area under the curve (ROC) statistics. Results The proportion of patients with any new ipsilateral DWI lesion was 51%. Advanced age (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01–1.11, p = 0.008), the presence of an ulcerated stenosis (OR 2.28: 95% CI 1.10–4.75; p = 0.027) or a lesion length > 1 cm (OR 2.65; 95% CI 1.33–5.28, p = 0.006) were independent risk factors for new ipsilateral DWI lesions. A 4 point score ranging from 0 to 4 (age ≥ 70 years = 1 point, age ≥ 80 years = 2 points, lesion length > 1 cm = 1 point, and presence of an ulcerated stenosis = 1 point) reliably predicted the incidence of this outcome parameter (ROC = 0.70, p Conclusions A simple risk score can be used to identify patients at a high risk for new DWI lesions as a possible surrogate of embolic complications after CAS.

CTP images analyzed with the Alberta stroke program early CT scale (ASPECTS) have been shown to be optimal predictors of clinical outcome. In this study we compared two biomarkers, the cerebral blood volume (CBV)-ASPECTS and the CTA-ASPECTS as predictors of clinical outcome after thrombectomy. Stroke patients with thrombosis of the M1 segment of the middle cerebral artery were included in our study. All patients underwent initial multimodal CT with CTP and CTA on a modern CT scanner. Treatment consisted of full dose intravenous tissue plasminogen activator, when applicable, and mechanical thrombectomy. Three neuroradiologists separately scored CTP and CTA images with the ASPECTS score. Sixty-five patients were included. Median baseline CBV-ASPECTS and CTA-ASPECTS for patients with favourable clinical outcome at follow-up were 8 [interquartile range (IQR) 8-9 and 7-9 respectively]. Patients with poor clinical outcome showed a median baseline CBV-ASPECTS of 6 (IQR 5-8, P

BACKGROUND AND PURPOSE: Several small case series reported a favorable clinical outcome for emergency stent placement in the extracranial internal carotid artery combined with mechanical thrombectomy in acute stroke. The rate of postinterventional symptomatic intracranial hemorrhages was reported to be as high as 20%. Therefore, we investigated the safety and efficacy of this technique in a large multicentric cohort. MATERIALS AND METHODS: The data bases of 4 German stroke centers were screened for all patients who received emergency stent placement of the extracranial internal carotid artery in combination with mechanical thrombectomy of the anterior circulation between 2007 and 2014. The primary outcome measure was the rate of symptomatic intracranial hemorrhage according to the European Cooperative Acute Stroke Study III criteria; secondary outcome measures included the angiographic revascularization results and clinical outcome. RESULTS: One hundred seventy patients with a median age of 64 years (range, 25–88 years) were treated. They presented after a median of 98 minutes (range, 52–160 minutes) with a median NIHSS score of 15 (range, 12–19). Symptomatic intracranial hemorrhages occurred in 15/170 (9%) patients; there was no statistically significant difference among groups pertaining to age, sex, intravenous rtPA, procedural timings, and the rate of successful recanalization. In 130/170 (77%) patients, a TICI score of ≥2b could be achieved. The in-hospital mortality rate was 19%, and 36% of patients had a favorable outcome at follow-up. CONCLUSIONS: Emergency stent placement in the extracranial internal carotid artery in combination with anterior circulation thrombectomy is effective and safe. It is not associated with a significantly higher risk of symptomatic intracranial hemorrhage compared with published series for mechanical thrombectomy alone.

Background In-stent restenosis (ISR) is an important factor endangering the long-term safety and efficacy of carotid artery angioplasty and stenting (CAS). It is plausible that soft vulnerable plaques are more likely to be injured during CAS procedure and are therefore more likely to initiate the cascade finally leading to ISR. The aim of this study was to investigate if plaque morphology detected by a simple applicable Duplex ultrasound score before CAS can be used as a predictor for ISR. Methods Within a prospectively collected single-centre CAS database of 281 patients (comprising 300 arteries) with high-grade carotid artery stenosis, who underwent CAS between May 2003 and January 2013, we conducted a nested case–control study. Plaque morphology before CAS was analysed by a blinded investigator and each parameter of the Total Plaque Risk Score (TPRS) as well as the whole score was evaluated with regard to its diagnostic validity for ISR. Results We analysed the data of 10 patients with ISR and 50 patients without ISR. There were no significant differences with respect to baseline characteristics, vascular risk factors, and degree of stenosis between patients with and without ISR. The duration of follow-up was longer in patients with ISR (p = 0.024) and these patients were more likely to show increased PSV (p = 0.012) immediately after CAS than patients without ISR. Neither individual parameters of the TPRS score nor the score as a whole were suitable as a diagnostic test for ISR development. Conclusions In the present study we could demonstrate that the non-contrast enhanced DUS of the pre-interventional plaque formation cannot be used as a predictor for the development of ISR. Evaluating a more sophisticated, but not routinely available approach e.g. by ultrasound based plaque perfusion imaging or CT based plaque analysis could be helpful in the future in order to assess the role of plaque morphology in the context of ISR development.

In acute stroke patients with large vessel occlusion, collateral blood flow affects tissue fate and patient outcome. The visibility of collaterals on computed tomography angiography (CTA) strongly depends on the acquisition phase, but the optimal time point for collateral imaging is unknown. We analysed collaterals in a time-resolved fashion using four-dimensional (4D) CTA in 82 endovascularly treated stroke patients, aiming to determine which acquisition phase best depicts collaterals and predicts outcome. Early, peak and late phases as well as temporally fused maximum intensity projections (tMIP) were graded using a semiquantitative regional leptomeningeal collateral score, compared with conventional single-phase CTA and correlated with functional outcome. The total extent of collateral flow was best visualised on tMIP. Collateral scores were significantly lower on early and peak phase as well as on single-phase CTA. Collateral grade was associated with favourable functional outcome and the strength of this relationship increased from earlier to later phases, with collaterals on tMIP showing the strongest correlation with outcome. Temporally fused tMIP images provide the best depiction of collateral flow. Our findings suggest that the total extent of collateral flow, rather than the velocity of collateral filling, best predicts clinical outcome. • Collateral flow visibility on CTA strongly depends on the acquisition phase • tMIP offers the best visualisation of the extent of collaterals • Outcome prediction may be better with tMIP than with earlier phases • Total extent of collaterals seems more important than their filling speed • If triggered too early, CTA may underestimate collateral flow

Introduction: Detection of paroxysmal atrial fibrillation (PAF) after an ischemic cerebrovascular event is of imminent interest, because oral anticoagulation as a highly effective secondary preventive treatment is available. Whereas permanent atrial fibrillation (AF) can be detected during routine electrocardiogram (ECG), longer detection duration will detect more PAF but might be resource consuming. Methods: Patients with acute ischemic stroke were prospectively investigated with an intensified algorithm to detect PAF (7 day Holter ECG, follow-up investigations after 90 days and one year, ISRCTN 46104198). Results: 281 patients were prospectively included in the study, 44 of which had to be excluded since they presented with permanent AF as diagnosed by ECG during admission and another 13 patients due other causes leaving 224 patients (mean age: 68.5 years, 58.5% male) as the final study population. 29 (12.9%) patients could be identified to have PAF during prolonged (median: 6.7 days IQR: 4.4-7.0) Holter monitoring, an additional 8 (3.6%) and 5 (2.2%) patients after follow-up investigations after 90 days and 1 year, respectively. In 182 patients no AF could be detected. Multivariate analysis identified advanced age (Odds ratio (OR) 1.04, 95% confidence interval (CI): 1.01-1.08), a higher initial NIH-SS (OR 1.10, 95% CI: 1.00-1.21) as well as clinical symptoms >24h (OR 3.45, 95% CI: 1.06-11.19) and a history of coronary artery disease (OR 2.74, 95% CI: 1.16-6.50) to be predictive for the detection of PAF. Receiver operation characteristics demonstrated an area under the curve of 0.783 for this model. Neither the results of blood analysis, duplex sonography, cerebral imaging nor routine echocardiography could be found to be independently associated with the detection of PAF. Conclusion: In acute stroke patients with advanced age, history of coronary artery disease, higher NIH-SS scores and ischemic stroke as the presenting event, a prolonged Holter ECG monitoring and follow-up is warranted to identify PAF. This could increase the detection rate of patients requiring anticoagulation and would be expected to reduce the risk of recurrent stroke in case of consequent anticoagulation of these patients.

Introduction In acute stroke patients with large vessel occlusion, demonstration of antegrade flow across thrombus on catheter angiography has been associated with higher rates of vessel recanalization after intra-arterial thrombolysis. 4-dimensional CT angiography (4-dimensional CTA) obtained from a perfusion CT exam has recently been used for non-invasive detection of antegrade flow across intracranial thrombus. We sought to determine whether antegrade flow on 4-dimensional CTA may predict early vessel recanalization after intravenous thrombolysis. Methods: From a prospectively collected database of acute stroke patients undergoing endovascular treatment, we identified patients with the following inclusion criteria: (1) anterior circulation vessel occlusion, (2) intravenous thrombolysis (“bridging lysis”) and (3) availability of thin-section 4-dimensional CTA reconstructed from a volume perfusion CT scan. 4-dimensional CTA was reviewed for antegrade flow traversing the occlusion site. Digital subtraction angiograms (DSA) obtained at the beginning of the endovascular procedure were assessed for early partial or complete recanalization after bridging thrombolysis. Results: 67 patients met the inclusion criteria. On 4-dimensional CTA, there was evidence of antegrade flow in 12 of 67 patients (17.9 %). Patients with and without antegrade flow had similar mean age (75±10 vs. 71±14 years; p=0.188), median presenting NIHSS (15.5 [range 8-26] vs. 17 [6-26]; p=0.249), mean time from symptom onset to i.v. thrombolysis (176±147 vs. 136±84; p=0.209) and mean time from i.v.thrombolysis to DSA (79±25 vs. 89±30 minutes; p=0.265). Early partial or complete recanalization on DSA was seen in 6 patients (9%) and was significantly more likely in patients with antegrade flow (4/12, 33.3%) versus those without (2/55, 3.6%; p=0.008 according to Fisher’s exact test). Conclusion: The finding of antegrade flow across thrombus on 4-dimensional CTA is associated with an increased rate of early recanalization after intravenous thrombolysis.

Diagnosis of paroxysmal atrial fibrillation (AF) in stroke patients is challenging, but highly clinically relevant. The percentage of stroke patients with permanent AF increases with age, but limited data are available for the age-dependent yield of paroxysmal AF by Holter monitoring. Patients with acute cerebral ischemia were included into the prospective observational Find-AF study. Patients free from AF at presentation received 7 day Holter monitoring. We calculated the percentage of otherwise undetected paroxysmal AF and the number needed to screen for age groups under 60 years, and in 5 year clusters from the age of 60 up to 85 and older. 272 patients were included, 43 (15.8 %) had AF at admission, 33 patients with paroxysmal AF were identified by 7 day Holter (n = 29) or medical history (n = 4).The yield of 7 day Holter ECG clearly increased with older age (p = 0.004)

Background and purpose Detection of paroxysmal atrial fibrillation (pAF) after an ischaemic cerebrovascular event is of imminent interest, because oral anticoagulation as a highly effective secondary preventive treatment is available. Whereas permanent atrial fibrillation (AF) can be detected during routine electrocardiogram (ECG), longer detection duration will detect more pAF but might be resource consuming. The current study tried to identify clinical predictors for pAF detected during long-term Holter ECG and clinical follow-up. Methods Patients with acute ischaemic stroke were prospectively investigated with an intensified algorithm to detect pAF (7-day Holter ECG, follow-up investigations after 90 days and 1 year). Results Two hundred and eighty-one patients were included, 44 of whom had to be excluded since they presented with permanent AF and another 13 patients had to be excluded due to other causes leaving 224 patients (mean age 68.5 years, 58.5% male). Twenty-nine (12.9%) patients could be identified to have pAF during prolonged Holter monitoring, an additional 13 (5.8%) after follow-up investigations. Multivariate analysis identified advanced age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01–1.08] as well as clinical symptoms >24 h (OR 5.17, 95% CI 1.73–15.48) and a history of coronary artery disease (OR 3.14, 95% CI 1.35–7.28) to be predictive for the detection of pAF. Conclusions In acute stroke patients with advanced age, history of coronary artery disease and clinical symptoms >24 h, a prolonged Holter ECG monitoring and follow-up is warranted to identify pAF. This could increase the detection rate of patients requiring anticoagulation and may be able to reduce the risk of recurrent stroke in the case of successful anticoagulation of these patients.

BACKGROUND AND PURPOSE: The PS is an innovative mechanical device designed to recanalize large-vessel occlusions by thrombus aspiration. The purpose of this study was to evaluate the effectiveness and neurologic outcome of patients treated with the PS in the setting of acute ischemic stroke. MATERIALS AND METHODS: A total of 91 patients with acute ischemic stroke due to large-vessel occlusion were treated with the PS and were included in our retrospective study. In 14 patients, only the PS was used for treatment; in 77 patients, mechanical recanalization was combined with IA and/or IV thrombolysis. Outcome was measured by using the mRS; recanalization was assessed with the TICI score. RESULTS: Mean patient age was 62 ± 19.4 years; the average NIHSS score at hospital admission was 17. Successful recanalization was achieved in 77% of patients. Median time from arterial puncture to recanalization was 49 minutes (quartiles, 31–86 minutes). At follow-up, 36% of the patients showed an NIHSS improvement of ≥10%, and 34% of the patients with an anterior circulation occlusion had an mRS score of ≤2, whereas only 7% of the patients with a posterior occlusion had a favorable outcome at follow-up. In total, 20 patients died during hospitalization; none of these deaths were device-related. CONCLUSIONS: In this study, the PS was an effective device for mechanical recanalization. Successful recanalization with the PS was associated with significant improvement of functional outcome in patients experiencing ischemic stroke secondary to anterior circulation occlusions.

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (

Background and Purpose— Angioplasty and stenting is increasingly being used for the treatment of intracranial stenoses. Based on a literature search (01/1998 to 04/2008) we sought to determine the immediate and long-term outcomes, as well as the durability of this procedure. Summary of Review— We identified 31 studies dealing with 1177 procedures, which had mainly been performed in patients with a symptomatic (98%) intracranial high-grade stenosis (mean: 78±7%) at high technical success rates (median: 96%; interquartile range [IQR]: 90% to 100%). The periprocedural minor or major stroke and death rates ranged from 0% to 50% with a median of 7.7% (IQR: 4.4% to 14.3%). Periprocedural complications were significantly higher in the posterior versus the anterior circulation (12.1%, versus 6.6%, P P =0.47, OR: 1.15, CI:0.76 to 2.05). Restenosis >50% occurred more frequently after the use of a self-expandable stent (16/92; 17.4%, mean follow-up time: 5.4 months) than a balloon-mounted stent (61/443; 13.8%, mean follow-up time: 8.7 months; P Conclusions— Although intracranial stenting appears to be feasible, adverse events vary widely. Against the background of the results of this review yielding a high rate of restenoses and no clear impact of new stent devices on outcome, the widespread application of intracranial stenting outside the setting of randomized trials and in inexperienced centers currently does not seem to be justified.

Atherosclerotic carotid artery stenosis is a major cause of disabling stroke or death. Although carotid endarterectomy (CEA) is currently considered to be the standard of care for patients with a severe symptomatic stenosis and selected patients with an asymptomatic carotid stenosis, carotid angioplasty and stenting (CAS) is increasingly being used as an alternative treatment modality. This article briefly summarizes the current trial data on CEA and CAS. More importantly, potential risk factors for CEA and CAS are reviewed and the complementary role of these techniques in the management of the individual patient is discussed.

To the Editor: We examined the article by Schillinger et al,1 in which the authors describe the results of a multicenter registry investigating the potential effect of open- versus closed-cell design stents on periprocedural complications after carotid artery stenting (CAS). In contrast to a previously published study,2 they found no association between stent design and the 30-day combined rate of transient ischemic attack, stroke and death. Aside from the stent design (ie, open-cell versus closed-cell) the length of the stent might be an additional factor associated with outcome after CAS. While the length of a stenosis has already been identified as a …

Background: Carotid angioplasty and stenting (CAS) may currently be recommended especially in younger patients with a high-grade carotid artery stenosis. However, evidence is accumulating that in-stent restenosis (ISR) could be an important factor endangering the long-term efficacy of CAS. The aim of this study was to investigate the influence of inflammatory serum markers and procedure-related factors on ISR as diagnosed with duplex sonography. Methods: We analyzed 210 CAS procedures in 194 patients which were done at a single university hospital between May 2003 and June 2010. Periprocedural C-reactive protein (CRP) and leukocyte count as well as stent design and geometry, and other periprocedural factors were analyzed with respect to the occurrence of an ISR as diagnosed with serial carotid duplex ultrasound investigations during clinical long-term follow-up. Results: Over a median of 33.4 months follow-up (IQR: 14.9–53.7) of 210 procedures (mean age of 67.969.7 years, 71.9% male, 71.0% symptomatic) an ISR of $70% was detected in 5.7% after a median of 8.6 months (IQR: 3.4–17.3). After multiple regression analysis, leukocyte count after CAS-intervention (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.02–1.69; p = 0.036), as well as stent length and width were associated with the development of an ISR during follow-up (OR: 1.25, 95% CI: 1.05–1.65, p = 0.022 and OR: 0.28, 95% CI: 0.09–0.84, p = 0.010). Conclusions: The majority of ISR during long-term follow-up after CAS occur within the first year. ISR is associated with periinterventional inflammation markers and influenced by certain stent characteristics such as stent length and width. Our findings support the assumption that stent geometry leading to vessel injury as well as periprocedural inflammation during CAS plays a pivotal role in the development of carotid artery ISR. peerReviewed

SummaryBackgroundCarotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA), especially in patients aged

Blood biomarkers may improve the performance in predicting early stroke outcome beyond well-established clinical factors. We investigated the value of growth-differentiation factor-15 (GDF-15) to predict functional outcome after 90 days in a prospectively collected patient cohort with symptoms of acute ischemic stroke. Two hundred eighty-one patients with symptoms of acute ischemic stroke were prospectively investigated. Serial blood samples for GDF-15 analysis were obtained after the admission of the patient, after 6 and 24 h. Primary outcome was the dichotomized modified ranking scale (MRS) 90 days after the initial clinical event. Within the final study population (264 patients, mean age 70.3 ± 12.7 years, 55.3% male), National Institutes of Health Stroke Scale (NIH-SS) [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.141–1.412, p