Neuronale alpha-adrenerge Stimulation von IFN-gamma, IL-6 und CXCL1 in murinen Milzen im Tiermodell der Arthritisspätphase

Es war vorbekannt, dass sympathische Nervenfasern mit Zytokin-produzierenden Zellen in der Milz von Mäusen in der Frühphase (Tag 32) des CIA-Modells kommunizieren (STRAUB). Diese Daten zeigten jeweils ausschließlich eine neuronale sympathische Regulation von IFN-y, CXCL1, IL-6 und TGF-ß. Allerdings könnte sich diese Schnittstelle in der Spätphase der CIA durch den Verlust sympathischer Nervenfasern und das Neuauftreten von NT-produzierenden Zellen ändern. Daher betrachten wir in dieser Arbeit die NT-abhängige Regulation von IFN-y, CXCL1, IL-6 und TGF-ß in der Milz von Mäusen, die sich in der Spätphase (Tag 58) der CIA befinden. Methodisch wurden hierfür Mäusemilzen am Tag 58 (46-68) nach Immunisierung in ca. 0,35mm dicke Scheibchen geteilt. Diese wurden in einem Superfusionsaufbau elektrischer Stimulation ausgesetzt, um so NT aus den sympathischen Nervenfasern freizusetzen. Durch den Einsatz von NT-Antagonisten und Kontrollbedingungen ohne ES konnte so der Einfluss der NT auf die Zytokinausschüttung untersucht werden. Es zeigte sich eine Hemmung von IFN-c, CXCL1, und IL-6, sowie eine Stimulation von TGF-b durch die ES. Diese Effekte waren deutlich schwächer ausgeprägt als in der Frühphase des CIA-Modells. Weiterhin zeigte sich eine ß-adrenerge Hemmung von IFN-y, IL-6 und TGF-ß, sowie eine Stimulation von CXCL1. Diese Effekte waren allesamt unabhängig von der ES und müssen daher als nicht-neuronal interpretiert werden. Neuronal vermittelt konnten wir eine α1/2 adrenerge Stimulation von IFN-y, CXCL1 und IL-6, sowie eine A1-adenosinerge Stimulation von TGF-ß beobachten. Daraus lässt sich ableiten, dass in der Spätphase des CIA-Modells der Einfluss nicht-neuronaler Zytokinregulation zunimmt, während der neuronale Einfluss abnimmt. Hierbei werden ß-adrenerge Effekte nicht-neuronal vermittelt, während α1/2 adrenerge Effekte offensichtlich neuronal vermittelt werden. Daraus lässt sich ableiten, dass zeitgleich mit der Veränderung der sympathischen Innervation der Milz sich auch die neuroimmunologische Wechselwirkung zwischen SNS und dem Immunsystem deutlich verändert

Pearls & Oy-sters: Bilateral Mononeuropathic Neuralgic Amyotrophy Triggered by Bartonella henselae Infection Responsive to Immunoglobulin.

We present a case of a cat owner with a scar on his right thenar eminence, followed by lymphadenopathy in the right axilla, general malaise and fever, and subsequent onset of bilateral neuralgic amyotrophy within one week. After a comprehensive workup, cat scratch disease caused by Bartonella henselae was confirmed serologically and adequately treated. Despite antibiotic treatment, the patient presented clinically with persistent bilateral, asymmetric neuropathy of the median nerve, predominantly the interosseous anterior nerve, which was confirmed by multifocal swelling and hyperintense signal of the nerves on T2-weighted MR neurography. Electrophysiological examination confirmed axonal median neuropathies bilaterally. After an unsuccessful steroid treatment trial, the patient showed an excellent and sustained response to intravenous immunoglobulin despite a delay from symptom onset to treatment of 10 months

Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry

Endovascular; Mechanical thrombectomy; StrokeEndovascular; Trombectomia mecànica; Accident cerebrovascularEndovascular; Trombectomía mecánica; Accidente cerebrovascularBACKGROUND AND PURPOSE: In acute ischaemic stroke (AIS) of the anterior circulation (AC) treated with mechanical thrombectomy (MT), data point to a decline of treatment effect with increasing time from symptom onset to treatment. However, the magnitude of the decline will depend on the clinical setting and imaging selection used. The aims of this study were (1) to evaluate the clinical effect of time to reperfusion (TTR); and (2) to assess the safety and technical efficacy of MT according to strata of TTR. METHODS: Using the retrospective multicentre BEYOND-SWIFT registry data (ClinicalTrials.gov identifier: NCT03496064), we compared safety and efficacy of MT in 1461 patients between TTR strata of 0-180 min (n = 192), 180-360 min (n = 876) and >360 min (n = 393). Clinical effect of TTR was evaluated using multivariable logistic regression analyses adjusting for pre-specified confounders [adjusted odds ratios (aOR) and 95% confidence intervals (95% CI)]. Primary outcome was good functional outcome (modified Rankin Scale: mRS 0-2) at day 90. RESULTS: Every hour delay in TTR was a significant factor related to mRS 0-2 (aOR 0.933, 95% CI 0.887-0.981) with an estimated 1.5% decreased probability of good functional outcome per hour delay of reperfusion, and mRS 0-1 (aOR 0.929, 95% CI 0.877-0.985). Patients with late TTR had lower rates of successful and excellent reperfusion, higher complication rates and number of passes. CONCLUSIONS: TTR is an independent factor related to long-term functional outcome. With increasing TTR, interventional procedures become technically less effective. Efforts should be made to shorten TTR through optimized prehospital and in-hospital pathways

Stent-Based Retrieval Techniques in Acute Ischemic Stroke Patients with and Without Susceptibility Vessel Sign.

BACKGROUND AND PURPOSE Randomized controlled trials have challenged the assumption that reperfusion success after mechanical thrombectomy varies depending on the retrieval techniques applied; however, recent analyses have suggested that acute ischemic stroke (AIS) patients showing susceptibility vessel sign (SVS) may respond differently. We aimed to compare different stent retriever (SR)-based thrombectomy techniques with respect to interventional outcome parameters depending on SVS status. METHODS We retrospectively reviewed 497 patients treated with SR-based thrombectomy for anterior circulation AIS. Imaging was conducted using a 1.5 T or 3 T magnetic resonance imaging (MRI) scanner. Logistic regression analyses were performed to test for the interaction of SVS status and first-line retrieval technique. Results are shown as percentages, total values or adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS An SVS was present in 87.9% (n = 437) of patients. First-line SR thrombectomy was used to treat 293 patients, whereas 204 patients were treated with a combined approach (COA) of SR and distal aspiration. An additional balloon-guide catheter (BGC) was used in 273 SR-treated (93.2%) and 89 COA-treated (43.6%) patients. On logistic regression analysis, the interaction variable of SVS status and first-line retrieval technique was not associated with first-pass reperfusion (aOR 1.736, 95% CI 0.491-6.136; p = 0.392), overall reperfusion (aOR 3.173, 95% CI 0.752-13.387; p = 0.116), periinterventional complications, embolization into new territories, or symptomatic intracerebral hemorrhage. The use of BGC did not affect the results. CONCLUSION While previous analyses indicated that first-line SR thrombectomy may promise higher rates of reperfusion than contact aspiration in AIS patients with SVS, our data show no superiority of any particular SR-based retrieval technique regardless of SVS status

Association of Chronic Covert Cerebral Infarctions and White Matter Hyperintensities With Atrial Fibrillation Detection on Post-Stroke Cardiac Rhythm Monitoring: A Cohort Study.

Background This study was conducted to explore the association of different phenotypes, count, and location of chronic covert brain infarctions (CBIs) with detection of atrial fibrillation (AF) on prolonged post-stroke cardiac rhythm monitoring (PCM). Methods and Results We conducted a cohort single-center study of consecutive first-ever ischemic stroke or transient ischemic attack patients undergoing PCM between January 2015 and December 2017. We blindly rated CBI phenotypes according to established definitions and white matter hyperintensities (WMHs) according to the age-related white matter changes rating scale. We used (multiple) regression models to assess the association of the imaging biomarkers and incident AF on PCM. A total of 795 patients (median [interquartile range]) aged 69 (57-78) years, 41% women, median National Institutes of Health Stroke Scale score 2 (0-5), median PCM duration 14 (7-14) days, and AF detection in 61 patients (7.7%) were included. On univariate analysis, WMHs (per point odds ratio, 1.35 [95% CI, 1.03-1.78]) but not CBIs (odds ratio, 0.90 [95% CI, 0.52-1.56]) were associated with AF detection. Neither CBI phenotype, count, nor location were associated with AF detection. After adjustment for age, hypertension, and stroke severity, neither increasing WMHs (per point adjusted odds ratio, 0.85 [95% CI, 0.60-1.20]) nor CBIs (adjusted odds ratio, 0.60 [95% CI, 0.33-1.09]) were independently associated with AF detection. Conclusions Although WMHs and CBIs represent surrogate biomarkers of vascular risk factors, neither WMHs nor CBIs, including their phenotypes, count, and location, were independently associated with AF detection on PCM. In patients with manifest ischemic stroke or transient ischemic attack, the presence of imaging biomarkers of chronic ischemic injury does not seem promising to further refine prediction tools for AF detection on PCM

Chronic cerebral infarctions and white matter lesions link to long-term survival after a first ischemic event: A cohort study.

BACKGROUND AND PURPOSE To investigate the association of different phenotypes, count, and locations of chronic covert brain infarctions (CBI) with long-term mortality in patients with first-ever manifest acute ischemic stroke (AIS) or transient ischemic attack (TIA). Additionally, to analyze their potential interaction with white matter hyperintensities (WMH) and predictive value in addition to established mortality scores. METHODS Single-center cohort study including consecutive patients with first-ever AIS or TIA with available MRI imaging from January 2015 to December 2017. Blinded raters adjudicated CBI phenotypes and WMH (age-related white matter changes score) according to established definitions. We compared Cox regression models including prespecified established predictors of mortality using Harrell's C and likelihood ratio tests. RESULTS A total of 2236 patients (median [interquartile range] age: 71 [59-80] years, 43% female, National Institutes of Health Stroke Scale: 2 [1-6], median follow-up: 1436 days, 21% death during follow-up) were included. Increasing WMH (per point adjusted Hazard Ratio [aHR] = 1.29 [1.14-1.45]), but not CBI (aHR = 1.21 [0.99-1.49]), were independently associated with mortality. Neither CBI phenotype, count, nor location was associated with mortality and there was no multiplicative interaction between CBI and WMH (p > .1). As compared to patients without CBI or WMH, patients with moderate or severe WMH and additional CBI had the highest hazards of death (aHR = 1.62 [1.23-2.13]). The Cox regression model including CBI and WMH had a small but significant increment in Harrell's C when compared to the model including 14 clinical variables (0.831 vs. 0.827, p < .001). DISCUSSION WMH represent a strong surrogate biomarker of long-term mortality in first-ever manifest AIS or TIA patients. CBI phenotypes, count, and location seem less relevant. Incorporation of CBI and WMH slightly improves predictive capacity of established risk scores

Multivariable Prediction Model for Futile Recanalization Therapies in Patients With Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES Very poor outcome despite intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) occurs in about 1 of 4 patients with ischemic stroke and is associated with a high logistic and economic burden. We aimed to develop and validate a multivariable prognostic model to identify futile recanalization therapies (FRT) in patients undergoing those therapies. MATERIALS AND METHODS Patients from a prospectively collected observational registry of a single academic stroke center treated with MT and/or IVT were included. The dataset was split into a training (N=1808, 80%) and internal validation (N=453, 20%) cohort. We used gradient boosted decision tree machine-learning models after k-NN imputation of 32 variables available at admission to predict FRT defined as modified Rankin-Scale (mRS) 5-6 at 3 months. We report feature importance, ability for discrimination, calibration and decision curve analysis. RESULTS 2261 patients with a median (IQR) age 75 years (64-83), 46% female, median NIHSS 9 (4-17), 34% IVT alone, 41% MT alone, 25% bridging were included. Overall 539 (24%) had FRT, more often in MT alone (34%) as compared to IVT alone (11%). Feature importance identified clinical variables (stroke severity, age, active cancer, prestroke disability), laboratory values (glucose, CRP, creatinine), imaging biomarkers (white matter hyperintensities) and onset-to-admission time as the most important predictors. The final model was discriminatory for predicting 3-month FRT (AUC 0.87, 95% CI 0.87-0.88) and had good calibration (Brier 0.12, 0.11-0.12). Overall performance was moderate (F1-score 0.63 ± 0.004) and decision curve analyses suggested higher mean net benefit at lower thresholds of treatment (up to 0.8). CONCLUSIONS This FRT prediction model can help inform shared decision making and identify the most relevant features in the emergency setting. While it might be particularly useful in low resource healthcare settings, incorporation of further multifaceted variables is necessary to further increase the predictive performance

Long‐Term Outcome and Quality of Life in Patients With Stroke Presenting With Extensive Early Infarction

Background The benefit of mechanical thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for short‐term outcomes is debatable and long‐term outcomes remain unknown. This retrospective, monocentric cohort study aimed to assess the association between reperfusion grade and the long‐term functional outcome measured with modified Rankin scale as well as the long‐term health‐related quality of life recorded at the last follow‐up in patients according to baseline ASPECTS (0–5 versus 6–10). Methods Deceased patients were identified from the Swiss population register and follow‐up telephone interviews were conducted with all surviving patients with stroke treated with mechanical thrombectomy between January 1, 2010, and December 31, 2018. Favorable outcome was defined as modified Rankin scale 0 to 3; health‐related quality of life was assessed using the 3‐level version of the EuroQol 5‐dimensional questionnaire. The EuroQol 5‐dimension utility index was calculated for statistical analyses. The reperfusion grade was core laboratory adjudicated using the expanded treatment in cerebral ischemia score. Adjusted odds ratios for the association between the reperfusion grade assessed by expanded treatment in cerebral ischemia and outcomes were calculated from multivariable logistic regression. Results Of the 1114 patients with available long‐term follow‐up records (median follow‐up, 3.67 years), 997 were included in the final analysis. Respectively, patients with low ASPECTS more often had complaints regarding mobility (67.1% versus 42.1%, P<0.001), self‐care (53.4% versus 31.2%, P<0.001), and usual activities (65.8% versus 41.4%, P<0.001) than patients with high ASPECTS, whereas reported pain/discomfort (65.7% versus 69.9%, P=0.49) and anxiety/depression (71.2% versus 78.9%, P=0.17) did not differ. In patients with low ASPECTS, increasing reperfusion grade was associated with a higher likelihood of long‐term favorable functional outcome (adjusted odds ratio, 1.43; 95% CI, 1.09–1.88 [P=0.01]) and health‐related quality of life (adjusted linear correlation coefficient, 0.05; 95% CI, 0.02–0.08) despite early extensive infarction. Conclusion Despite low baseline ASPECTS, a higher reperfusion grade results in better functional outcomes and may improve health‐related quality of life in the long term

Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.

PURPOSE Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. METHODS We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. RESULTS In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). CONCLUSION Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy : a systematic review and meta-analysis of observational data

Background Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin ScalePeer reviewe