Ilko L. Maier

Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.

Background Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans. Methods 625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models. Results 553 (88.3%) patients were admitted with ischemic stroke, the remaining 72 (11.7%) had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5–16) points. 301 (48.2%) patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77–1.30, p = 0.995). Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43–0.98, p = 0.040). 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65–2.77, p = 0.425), while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20–3.10, p = 0.006). Conclusions Beta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.

Effects of Workflow Optimization in Endovascularly Treated Stroke Patients – A Pre-Post Effectiveness Study

Endovascular treatment of acute ischemic stroke has become standard of care for patients with large artery occlusion. Early restoration of blood flow is crucial for a good clinical outcome. We introduced an interdisciplinary standard operating procedure (SOP) between neuroradiologists, neurologists and anesthesiologists in order to streamline patient management. This study analyzes the effect of optimized workflow on periprocedural timings and its potential influence on clinical outcome. Data were extracted from a prospectively maintained university hospital stroke database. The standard operating procedure was established in February 2014. Of the 368 acute stroke patients undergoing endovascular treatment between 2008 and 2015, 278 patients were treated prior to and 90 after process optimization. Outcome measures were periprocedural time intervals and residual functional impairment. After implementation of the SOP, time from symptom onset to reperfusion was significantly reduced (median 264 min prior and 211 min after SOP-introduction (IQR 228–32 min and 161–278 min, respectively); P<0.001). Especially faster supply of imaging and prompt transfer of patients to the angiography suite contributed to this effect. Time between hospital admission and groin puncture was reduced by half after process optimization (median 64 min after versus 121 min prior to SOP-introduction (IQR 54–77 min and 96–161 min, respectively); P<0.001). Clinical outcome was significantly better after workflow optimization as measured with the modified Rankin Scale (common odds ratio (OR) 0.56; 95% CI 0.32–0.98; P = 0.038). Optimization of workflow and interdisciplinary teamwork significantly improved the outcome of patients with acute ischemic stroke due to a significant reduction of in-hospital examination, transportation, imaging and treatment times.

Comparing different thrombectomy techniques in five large-volume centers: a ‘real world’ observational study

Background and purpose Thrombectomy has become the standard of care for acute ischaemic stroke due to large vessel occlusion. Aim of this study was to compare the radiological outcomes and time metrics of the various thrombectomy techniques. Methods In this retrospective, multicenter study we analysed the data of 450 patients with occlusion of the anterior circulation, treated in five high-volume center from 2013 to 2016. The treatment techniques were divided in three categories: first-pass use of a large-bore aspiration-catheter; first-pass use of a stent-retriever; and primary combined approach (PCA) of an aspiration-catheter and stent-retriever. Primary endpoints were successful reperfusion and groin to reperfusion time. Secondary endpoints were the number of attempts and occurrence of emboli in new territory (ENT). The primary analysis was based on the intention to treat groups (ITT). Results The ITT-analysis showed significantly higher reperfusion rates, with 86% of successful reperfusion in the PCA-group compared with 73% in the aspiration group and 65% in the stent-retriever group. There was no significant difference in groin to reperfusion time regarding the used technique. The secondary analysis showed an impact of the technique on the number of attempts and the occurrence of ENTs. Lowest ENT rates and attempts were reported with the combined approach. Conclusions The combined first-pass deployment of a stent-retriever and an aspiration-catheter was the most effective technique for reperfusion of anterior circulation large vessel occlusion. Our results correlate with the latest single-centrere studies, reporting very high reperfusion rates with PCA variations.

One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion Times

Background and Purpose— Intrahospital time delays significantly affect the neurological outcome of stroke patients with large-vessel occlusion. This study was conducted to determine whether a one-stop management can reduce intrahospital times of patients with acute large-vessel occlusion. Methods— In this observational study, we report the first 30 consecutive stroke patients imaged and treated in the same room. As part of our protocol, we transported patients with a National Institutes of Health Stroke Scale score of ≥10 directly to the angio suite, bypassing multidetector computed tomography (CT). Preinterventional imaging consisted of noncontrast flat detector CT and flat detector CT angiography, acquired with an angiography system. Patients with large-vessel occlusions remained on the angio table and were treated with mechanical thrombectomy; patients with small artery occlusions were treated with intravenous thrombolysis, whereas patients with an intracranial hemorrhage and stroke mimics were treated as per guidelines. Door-to-groin puncture times were recorded and compared with our past results. Results— Thirty patients were transferred directly to our angio suite from June to December 2016. The time from symptom onset to admission was 105 minutes. Ischemic stroke was diagnosed in 22 of 30 (73%) patients, 4 of 30 (13.5%) had an intracranial hemorrhage, and 4 of 30 (13.5) were diagnosed with a Todd’s paresis. Time from admission to groin puncture was 20.5 minutes. Compared with 44 patients imaged with multidetector CT in the first 6 months of 2016, door-to-groin times were significantly reduced (54.5 minutes [95% confidence interval, 47–61] versus 20.5 minutes [95% confidence interval, 17–26]). Conclusions— In this small series, a one-stop management protocol of selected stroke patients using latest generation flat detector CT led to a significant reduction of intrahospital times.

Bridging-therapy with intravenous recombinant tissue plasminogen activator improves functional outcome in patients with endovascular treatment in acute stroke ☆

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 50min; 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.

Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial

Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65–3.79, p = 0.317), the short-term (OR 0.64, 0.26–1.58, p = 0.327) or long-term diagnosis of AF (OR 0.72, 0.31–1.68, p = 0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.

Validation of collateral scoring on flat-detector multiphase CT angiography in patients with acute ischemic stroke

Background The pivotal impact of collateral circulation on outcomes in endovascular therapy has fueled the development of numerous CTA collateral scales, yet synchronized validation with conventional angiography has never occurred. We validated multiphase flat-detector CTA (mpFDCTA) for collateral imaging in patients undergoing endovascular stroke treatment. Materials and methods Consecutive acute ischemic stroke patient data, including mpFDCTA shortly followed by digital subtraction angiography (DSA), in the setting of acute ICA- or MCA-occlusions were analyzed. An independent core lab scored mpFDCTA with an established collateral scale and separately graded American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score on DSA, blind to all other data. Results 24 consecutive cases (age 76.7 ± 7.3 years; 58.3% women; baseline NIHSS median 17 (4–23)) of acute ICA- or MCA-occlusion were analyzed. Time from mpFDCTA to intracranial DSA was 23.04 ± 7.6 minutes. Median mpFDCTA collateral score was 3 (0–5) and median DSA ASITN collateral score was 2 (0–3), including the full range of potential collateral grades. mpFDCTA and ASITN collateral score were strongly correlated (r = 0.86, p<0.001). mpFDCTA provided more complete collateral data compared to selective DSA injections in cases of ICA-occlusion. ROC analyses for prediction of clinical outcomes revealed an AUC of 0.76 for mpFDCTA- and 0.70 for DSA ASITN collaterals. Conclusions mpFDCTA in the angiography suite provides a validated measure of collaterals, offering distinct advantages over conventional angiography. Direct patient transfer to the angiography suite and mpFDCTA collateral grading provides a novel and reliable triage paradigm for acute ischemic stroke.

High Systolic Blood Pressure after Successful Endovascular Treatment Affects Early Functional Outcome in Acute Ischemic Stroke

Background: Endovascular treatment (EVT) has been shown to significantly improve functional outcome in patients with acute large cerebral vessel occlusions. To date, no evidence-based recommendations on blood pressure management after successful EVT exist. Previous studies showed an association between high pre-EVT systolic blood pressure (SBP) and functional outcome, but do not answer the question on how to manage blood pressure after successful recanalization. The purpose of this study was to determine the role of blood pressure measurements as a predictor for early functional outcome in patients with successful EVT. Methods: Prospectively derived data from patients with acute large vessel occlusion within the anterior circulation and EVT was analyzed in this monocentric study. Mean systolic- and maximum SBP as well as SBP-peaks have been obtained for the first 24 h after successful EVT. Predictive value of SBP for discharge modified Rankin Scale (mRS) ≤2 has been investigated using logistic regression models. Results: From 168 patients with successful EVT, 74 (44%) had a favorable outcome with an mRS ≤2. Mean- (127 vs. 131 mm Hg, p = 0.035) and maximum SBP (157 vs. 169 mm Hg, p < 0.001) as well as the number of SBP-peaks (0 vs. 1.5, p = 0.004) were lower in patients with favorable outcomes. Multivariable logistic regression showed high mean- and maximum SBP to predict unfavorable outcomes. Cutoff mean SBP was 141 mm Hg and maximum SBP 159 mm Hg. Conclusions: High SBP in the first 24 h after recanalization of acute anterior cerebral vessel occlusions is associated with unfavorable functional outcome. Interventional studies are needed to determine the role of SBP management as a modifiable parameter in the early phase after successful EVT.

Influence of beta-blocker therapy on the risk of infections and death in patients at high risk for stroke induced immunodepression

Background Stroke-induced immunodepression is a well characterized complication of acute ischemic stroke. In experimental studies beta-blocker therapy reversed stroke-induced immunodepression, reduced infection rates and mortality. Recent, heterogeneous studies in stroke patients could not provide evidence of a protective effect of beta-blocker therapy. Aim of this study is to investigate the potential preventive effect of beta-blockers in subgroups of patients at high risk for stroke-induced immunodepression. Methods Data from a prospectively derived registry of major stroke patients receiving endovascular therapy between 2011–2017 in a tertiary stroke center (University Medical Center Göttingen. Germany) was used. The effect of beta-blocker therapy on pneumonia, urinary tract infection, sepsis and mortality was assessed using multivariate logistic regression analysis. Results Three hundred six patients with a mean age of 72 ± 13 years and a median NIHSS of 16 (IQR 10.75–20) were included. 158 patients (51.6%) had pre-stroke- and continued beta-blocker therapy. Beta-blocker therapy did not reduce the incidence of pneumonia (OR 0.78, 95% CI 0.31–1.92, p = 0.584), urinary tract infections (OR 1.51, 0.88–2.60, p = 0.135), sepsis (OR 0.57, 0.18–1.80, p = 0.334) or mortality (OR 0.59, 0.16–2.17, p = 0.429). Strokes involving the insula and anterio-medial cortex increased the risk for pneumonia (OR 4.55, 2.41–8.56, p<0.001) and sepsis (OR 4.13, 1.81–9.43, p = 0.001), while right hemispheric strokes increased the risk for pneumonia (OR 1.60, 0.92–2.77, p = 0.096). There was a non-significantly increased risk for urinary tract infections in patients with beta-blocker therapy and insula/anterio-medial cortex strokes (OR 3.12, 95% CI 0.88–11.05, p = 0.077) with no effect of beta-blocker therapy on pneumonia, sepsis or mortality in both subgroups. Conclusions In major ischemic stroke patients, beta-blocker therapy did not lower post-stroke infection rates and was associated with urinary tract infections in a subgroup with insula/anterio-medial strokes.

Outcome Prediction Using Perfusion Parameters and Collateral Scores of Multi-Phase and Single-Phase CT Angiography in Acute Stroke: Need for One, Two, Three, or Thirty Scans?

Background and Purpose Collateral status is an important factor determining outcome in acute ischemic stroke (AIS). Hence, different collateral scoring systems have been introduced. We applied different scoring systems on single- and multi-phase computed tomography (CT) angiography (spCTA and mpCTA) and compared them to CT perfusion (CTP) parameters to identify the best method for collateral evaluation in patients with AIS. Methods A total of 102 patients with AIS due to large vessel occlusion in the anterior circulation who underwent multimodal CT imaging and who were treated endovascularly were included. Collateral status was assessed on spCTA and mpCTA using four different scoring systems and compared to CTP parameters. Logistic regression was performed for predicting favorable outcome. Results All collateral scores correlated well with each other and with CTP parameters. Comparison of collateral scores stratified by extent of perfusion deficit showed relevant differences between groups (P<0.01 for each). An spCTA collateral score discriminated best between favorable and unfavorable outcome as determined using the modified Rankin Scale 3 months after stroke. Conclusions Collateral status evaluated on spCTA may suffice for outcome prediction and decision making in AIS patients, potentially obviating further imaging modalities like mpCTA or CTP.