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Background And Aims

There is still conflicting evidence whether reperfusion is associated with a lower risk for cerebral edema (CED) in acute ischemic stroke. We investigated the association of reperfusion with development of early CED after stroke thrombectomy.

Methods

From SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of intracranial internal carotid or middle cerebral artery (M1 or M2). Reperfusion was defined as mTICI >=2b. Primary outcome was moderate or severe CED, defined as focal brain swelling >=1/3 of the hemisphere on imaging scans at 24 hours. We performed log link binary regression while adjusting for baseline variables. Effect modification of Severe hemispheric syndrome (SHS) defined as NIH Stroke Scale score>15 at baseline was explored.

Results

In total, 4640 patients, median age 70 years and median NIHSS 16, were included. Of these, 3971 (85.6%) had reperfusion. Moderate or severe CED was less frequent among patients that had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p<0.05, crude Risk Ratio (RR) 0.42 (95% CI 0.37-0.49), and adjusted RR 0.53 (95% CI 0.46-0.61). The interaction terms between SHS and reperfusion were significant (p<0.01), indicating that SHS weakens the association between reperfusion and lower risk of CED. Adjusted RR for CED with reperfusion was 0.60 (0.51-0.70) among patients with SHS and 0.33 (0.25-0.43) among patients without SHS.

Conclusions

In patients with large artery occlusion stroke that underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. The RR reduction was less favorable in patients with SHS.

Background And Aims

Cerebral edema (CED) in ischemic stroke can worsen prognosis. In large hemispheric infarcts (LHI) with severe CED, about 70% of patients die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia.

Methods

Observational study based on SITS-International Treatment Registry (2003-2019). Severe hemispheric syndrome (SHS) at baseline and LHI at 24 hours were defined as NIHSS>15. Outcomes were moderate/severe CED, detected using CT or MRI, functional independence (mRS 0-2) and death at 3 months.

Results

8560 patients presented with SHS and LHI. 7035 (82.2%) received IV thrombolysis (IVT), 903 (10.5%) IVT+Thrombectomy and 622 (7.3%) thrombectomy alone. Median age was 77 and NIHSS 21 (18-23). Of 7949 patients with available CED data, 3780 (47.6%) had any CED and 2297 (28.9%) were moderate/severe. In the multivariable analysis, age<50 years (relative risk, RR=1.54), signs of acute infarct (RR=1.29), hyperdense artery sign (RR=1.39), blood glucose>128.5 mg/dl (RR=1.21) and decreased level of consciousness (RR=1.14) were associated with moderate/severe CED (for all p<0.05). Patients with any CED were less likely to achieve functional independence (aOR 0.36, 95%CI 0.24-0.53) and patients with severe CED presented a higher risk of 3-month death (aOR 3.94, 95%CI 3-5.13).

Conclusions

In patients with extensive ischemia, the most important predictors for moderate/severe CED development were young age, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans and decreased level of consciousness. Any CED was associated with worse functional outcome and severe CED was associated with a higher risk of death at 3 months.

Trial Registration Number

Not applicable

Background And Aims

Serum amyloid - A Protein (SAA) has shown in previous studies that it may help to identify patients at risk of infections in order to guide adequate therapy-decisions in an earlier state. The aim of this study was to independently validate SAA, to predict post stroke infections.

Methods

We measured SAA within 24h of stroke-onset in the BIOSIGNAL (Biomarker signature of stroke etiology) study. Primary outcome measure was any post stroke infection occurring during hospitalization, defined by the criteria of the U.S. Centers for Disease Control and Prevention. Patients with infection history on admission were excluded.

Results

Out of 1142 stroke patients, 19% (n=221) developed an infection. After adjusting for all significantly associated predictors of infection in the univariate analysis, SAA remained an independent predictor (adj. OR=1.23 [95% CI, 1.11 – 1.37], P=0.000). Adding SAA to the best regression model without the biomarker, the discriminatory accuracy improved from 0.83 [95% CI, 0.80 – 0.87] to 0.84 [95% CI, 0.81 – 0.87] p<0.0000.

Conclusions

SAA measured on admission is an independent predictor of post-stroke infection. SAA improved the risk stratification of patients who developed an infection in an external validation cohort.

Trial Registration Number

NCT02274727

Group Name

The MR CLEAN-NO IV investigators

Background And Aims

A feared outcome of intravenous alteplase (IVT) as treatment for acute ischemic stroke is intracranial hemorrhage (ICH). ICH can remain asymptomatic or present as symptomatic intracranial hemorrhage (sICH). We determined whether IVT, revascularization or both are associated with any ICH and sICH in the MR CLEAN NO-IV trial. This trial randomized patients with acute ischemic stroke due to large vessel occlusion with an onset of less than 4.5 hours, to IVT followed by EVT or EVT alone.

Methods

We included patients from the MRCLEAN NO-IV trial with follow-up imaging (n=487). ICH was classified according to the Heidelberg bleeding classification. eTICI 2b/3 was considered successful reperfusion. Multinomial and binary logistic regression were used to determine the association of IVT and reperfusion with any ICH and sICH.

Results

Figure 1 represents the number of any ICH per treatment group and reperfusion. Of the 13 patients with subarachnoid hemorrhage, 3 were major/catastrophic and one was caused by a perforation. Thirty patients had sICH. IVT was not significantly associated with any ICH or with sICH (Hemorrhagic infarction 1 OR:0.89,95CI:0.53-1.51, hemorrhagic infarction 2 OR:1.50,95CI:0.75-2.97, parenchymal hematoma 1 OR:1.64,95CI:0.37-7.36, parenchymal hematoma 2 OR:1.24,95CI:0.55-2.82, subarachnoid hemorrhage OR:1.30,95CI:0.44-3.83)(sICH OR:1.12,95CI:0.53-2.37). Successful reperfusion was only associated with less subarachnoid hemorrhage (eTICI2b/3: OR:0.23,95CI:0.07-0.70).

Figure 1. Number of patients with any ICH. Reperfusion data was missing for 46 patiemts.

Conclusions

Reperfusion nor treatment with IVT were associated with an increased risk of any ICH or sICH. However, in patients without successful reperfusion subarachnoid hemorrhage was more commonly observed probably due to a more complex procedure.

Trial Registration Number

ISRCTN80619088

Group Name

Mehwish Younas1,2, Laura McCulloch6, Ruth Stephens1,2, Barry W McColl6, Craig J. Smith3,4,5, John Grainger1,2, Stuart M. Allan1,5

1Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK 3 Greater Manchester Comprehensive Stroke Centre, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK 4Division of Cardiovascular Sciences, Lydia Becker Institute of Immunology and Inflammation, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK 5 Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester 6UK Dementia Research Institute, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK

Background And Aims

Alterations in immune response can contribute to stroke associated infections (SAI). Human marginal zone-like B cells (MZ-like B cells) are innate-like B cells that provide a rapid and relatively low affinity response by producing IgM. We investigated whether alterations to MZ-like B cells in the acute ischaemic stroke determine their potential contribution to the onset of SAI.

Methods

Peripheral blood cells (PBMCs) were isolated from acute ischemic stroke patients (n=44; median age 69, NIHSS 8-26) at 24-48 hours after stroke onset and from age and sex matched non-stroke controls (n=23; age 65). B cells populations frequencies were anaylsed by Flow cytometry data analysis.

Results

We observed a significant loss of MZ like B cells (CD27⁺IgD⁺IgM^highCD1C⁺CD43-) in stroke patients (p=0.0002) in comparison to controls, which correlated with stroke severity and infection status of patients. IgM concentration was similarly suppressed in plasma of infected patients and correlated with the frequency of MZ B cells. We found a decreased IgM expression on these cells.

ScRNA seq and flow cytometry data showed relatively high expression of β2-adrenergic receptors (β2-AR) on MZ like B cells. This suggests adrenergic signalling may have a role in modulating MZ-like B cells after stroke. Ex vivo and in vitro experiments on B cells confirmed noradrenaline not only increased apoptosis in MZ-like B cells but also induced a dysfunctional phenotype with altered cytokines like IL-10, IL-6, TNF-β and IgM antibody.

Conclusions

The altered composition and function of innate-like B cells after stroke may contribute to infection susceptibility, thus, highlighting an important pathway for intervention to prevent SAI.

Trial Registration Number

Not applicable

Background And Aims

Post-stroke infections are associated with long-term poor recovery. The biological mechanisms underlying these infections are poorly understood. We aimed to find genetic risk factors and to study the biological mechanisms associated with post-stroke respiratory infections.

Methods

We studied 2,003 ischemic stroke patients with respiratory infection data collected during hospitalization and 4,104 population controls (discovery cohort). We performed a Genome-Wide Association Study (GWAS) of 7,155,935 single-nucleotide polymorphisms (SNPs) using SNPTEST software. PLINK software was used for quality controls. Analyses were adjusted for age, sex, stroke severity (NIHSS score) and ancestry. We used an independent cohort of 269 ischemic stroke patients with respiratory infection data to replicate the significant results from the discovery cohort.

Results

We identified five genetic variants from five independent loci located in four different chromosomes (Chr2, Chr5, Chr8 and Chr15) associated with post-stroke respiratory infection (p < 5x10^-08). The SNP from Chr2 was replicated in the replication cohort (discovery cohort p < 2,43 x10^-08; replication cohort p < 1,19x10^-06). This SNP was previously associated with lung diseases and hematological traits, such as eosinophil counts. The nearest gene regulates Natural Killer (NK) cell development and NK cell activation during pulmonary bacterial infections.

Conclusions

We found a genetic variation associated with post-stroke respiratory infection. The nearest gene has been associated with NK cell activation during pulmonary infections, revealing potential candidate drug targets and biomarkers for personalized prevention strategies.

Background And Aims

We aimed to investigate if advanced analytical methods could out-perform existing risk scores for predicting the risk of Stroke Associated Pneumonia (SAP) within the first 7 days after hospital admission.

Methods

Data from the UK Sentinel Stroke National Audit Program (SNAPP) between 2013 to June 2019 were used. XGBoost, Logistic Regression (LR) with elastic net, and LR with elastic net and interaction term models with 30 variables were developed using 80% randomly selected admissions from 2013 to 2018, internally validated on the 20% remaining admissions, and temporally validated on all admissions from 2019. The prestroke Independence [modified Rankin scale], Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was used as reference model. Performance of the risk prediction models was evaluated in terms of accuracy (Brier score), discrimination, calibration, and net reclassification and Decision-curve analyses.

Results

Data from 483,561 patients were used, with an overall 7-day SAP rate of 8.59%. All developed models outperformed ISAN (area under the ROC curve (AUC) 0.740, 95% confidence interval [CI]: 0.732 to 0.749) on the 2019 temporal validation set with XGBoost achieving the highest AUC (0.782, 95% CI: 0.775 to 0.790). More results will be presented at the conference.

Conclusions

Risk prediction of SAP was improved with state-of-the-art risk prediction methods using more variables compared to the existing ISAN score. The gain in accuracy from complex prediction models may not be enough to justify their use in clinical settings compared to a simple risk score that can be calculated without computers.

Background And Aims

Only limited established risk-factors exist for the prediction of post stroke delirium (PSD) after acute ischemic stroke (AIS). S100B is a marker of neuronal damage and astrocyte activation and may early indicate disturbed blood-brain-barrier permeability. We aim to evaluate the predictive value of S100B for the development of PSD.

Methods

We determined S100B levels within 24h after symptom-onset in a single-center subcohort of 1154 AIS patients from the BIOSIGNAL cohort-study (NCT02274727). Participants were regularly monitored for the development of PSD (according to DSM-IV). The independent prognostic utility of S100B for PSD was assessed with logistic regression and Cox proportional hazard regression models including established risk-factors for PSD (age, sex, known dementia, NIHSS on admission).

Results

PSD occurred in 137 of 1154 patients (11,9 %) within 30 days after symptom onset. Circulating S100B levels were independently associated with PSD after adjustment for established risk-factors (OR 2.39; 95%-CI 1.40-4.07; p=0.001 for each log₁₀S100B unit increase). Adding S100B to the clinical model increased the AUC of the ROC curve from 0.72 (95%-CI 0.68-0.76) to 0.73 (95%-CI 0.69-0.77), p<0.01). Competing risk hazards regression confirmed that S100B levels were associated with a higher risk for the development of PSD (HR 2.13, 95%-CI 1.33-3.41, p<0.01). In the subgroup of patients with available MRI-DWI data, the associations remained significant after adjustment for categorized lesion size.

Conclusions

Circulating S100B is independently associated with a higher risk of developing PSD in AIS patients. Thus S100B may be clinically useful for early risk-stratification towards development of PSD.

Trial Registration Number

NCT02274727