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Introduction by the Convenors
STRATEGIC INFARCT LOCATIONS FOR POST-STROKE DEPRESSIVE SYMPTOMS: A LESION- AND DISCONNECTION-SYMPTOM MAPPING STUDY
Abstract
Background And Aims
Depression is the most common neuropsychiatric complication after stroke. Infarct location is associated with post-stroke depressive symptoms (PSDS), but it remains debated which brain structures are critically involved. We performed a large-scale lesion-symptom mapping study to identify infarct locations, and white matter disconnections, associated with PSDS.
Methods
We included 553 patients (age 69±11y, 42%F) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale. Multivariate support vector regression-based analyses were performed on voxels (SVR-VLSM) and predefined regions of interest (SVR-ROI) to relate infarct location to PSDS, with correction for potential confounders. We externally validated our findings in an independent stroke cohort (N= 459) using linear regression. Finally, disconnectome-based analyses were performed using SVR-VLSM, in which disconnections resulting from the infarct were analyzed instead of the infarct itself.
Results
Infarcts in the right amygdala, right hippocampus and right pallidum were associated with PSDS, independently from confounders (Fig.1). External validation (N=459) confirmed associations between infarcts in the right amygdala (standardized beta [stB]=-0.15, p=0.001) and pallidum (stB=-0.14, p=0.002), but not the right hippocampus (stB=-0.03, p=0.478), and PSDS. Disconnectome-based analyses revealed that disconnections in the right parahippocampal white matter, right thalamus and pallidum, and right anterior thalamic radiation were associated with PSDS (Fig.2).
Conclusions
Infarcts in the right amygdala and pallidum, and disconnections of right limbic and frontal cortico-basal ganglia-thalamic circuits, are associated with PSDS. Our findings provide a comprehensive and integrative picture of strategic infarct locations for PSDS, and shed new light on pathophysiological mechanisms of depression.
Trial Registration Number
Not applicable
BRAIN ATROPHY AND ENDOVASCULAR TREATMENT EFFECT IN ACUTE ISCHEMIC STROKE
Abstract
Group Name
the MR CLEAN Trial Investigators
Background And Aims
Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke (AIS). Our aim was to investigate whether the effect of endovascular treatment (EVT) is modified by brain atrophy in patients with AIS due to a large vessel occlusion (LVO).
Methods
Data from the MR CLEAN trial was used including patients with AIS due to LVO in the anterior circulation within 6 hours after symptom onset randomized to EVT (intervention) or no-EVT (control). Total brain volume (TBV) and intracranial volume (ICV) was assessed on baseline non-contrast computed tomography (n=444) using a validated automated segmentation method. Degree of atrophy was determined as the proportion of brain volume lost in relation to head size (1-TBV/ICV)x100%, analyzed on a continuous scale and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale estimated as the adjusted common odds ratio (acOR). Treatment effect modification was tested by adding an interaction term between treatment allocation and brain atrophy (as continuous variable).
Results
Benefit of EVT was seen irrespective of brain atrophy with shifts towards better come across all tertiles (acOR, 1.49 [95% CI: 0.79-2.79] in the lowest tertile versus 2.09 [95% CI: 1.12-3.89] in the middle tertile 2.79 [95% CI: 1.47-5.32] in the highest tertile). Brain atrophy did not modify EVT effect on functional outcome (P interaction = 0.06).
Conclusions
Benefit of EVT was seen across the entire range of atrophy, demonstrating that brain atrophy should not be used as an argument to withhold EVT.
Trial Registration Number
The MR CLEAN trial is registered under number NTR1804 in the Dutch trial register and under ISRCTN10888758 in the ISRCTN register.
INCREASED IN HOSPITAL MORTALITY IN STROKE DURING THE COVID-19 ERA AND RELATED FACTORS
Abstract
Background And Aims
The COVID-19 pandemic has had enormous implications for stroke care. We aim to analyze its impact in stroke outcomes and mortality in two comprehensive stroke centers (CSC) from the Catalonian network.
Methods
We studied all stroke patients admitted during 2020 and compared them with the admissions of 2019. Clinical and functional outcomes (mRS at discharge, in-hospital complications and mortality) were analyzed. Related factors, including SARS-CoV-2 infection, were determined.
Results
A total of 2674 stroke patients were admitted in 2020, and 2652 during 2019. A higher number of unknown-onset strokes (45% vs 40%, p<0.01), ASPECTS<7 (8.3% vs 5.7%, p=0.03) and longer time from symptoms-onset to hospital-admission (median: 337 vs. 272min, p<0.01) were detected during 2020. Conversely, no significant differences appeared in stroke code activation (61.5% vs 62.5%), stroke subtype (ICH 9.1% vs 8.9%), severity (median NIHSS: 4 vs 5), pre-morbid mRS (mRS<3 81.8% vs 80.2%) or other relevant clinical characteristics nor reperfusion treatments (23.8% vs 23.9%). In-hospital complications and discharge-mRS were similar. However, we observed higher in-hospital mortality in 2020 (9.6 vs 6.6%,p<0.001). An adjusted regression model pointed pre-morbid mRS, baseline NIHSS, ASPECTS and in-hospital complications (OR 1.26, 1.14, 0.87 and 1.38 respectively, p<0.01) as independent predictors of mortality. SARS-CoV-2 infection (3.7% of strokes in 2020) was not predictor of mortality; in fact, these patients showed similar outcomes than the remaining 2020 strokes.
Conclusions
The increased in-hospital mortality detected in 2020 in our series may be due to pandemic-related delays in stroke detection and hospital arrival rather than the direct effect of COVID-19.
STROKE RECURRENCE IN DENMARK: RISK AND MORTALITY
Abstract
Background And Aims
Knowledge on the risk and prognosis of stroke recurrence is limited. We examined risks of stroke recurrence and mortality after first and recurrent stroke.
Methods
Danish patients (≥18 years) with a first-time ischemic stroke (IS; n = 105,527) or intracerebral hemorrhage (ICH; n = 13,387) during 2004–2018 were identified from the Danish Stroke Registry and the Danish National Patient Registry. Using competing risk methods, we computed absolute risks, risk differences, and odds ratios of stroke recurrence separately for each stroke subtype and within patient subgroups. Mortality was assessed with the Kaplan-Meier estimator.
Results
The 1-year and 10-year risks of recurrence were 4% and 13% for IS and 2% and 7% for ICH. For IS, the risk increased marginally with age and was higher for men than for women, for milder first-time stroke than for more severe, and for obese than for normal weight patients. Essen risk scores predicted recurrence in a dose-response manner. For ICH, risks were similar between sexes and did not increase with body mass index and Essen risk score. For IS, the 1-year and 10-year risks of mortality were 17% and 56% after first-time stroke and 22% and 69% after recurrent stroke; corresponding estimates for ICH were 37% and 69% after a first-time event and 41% and 82% after a recurrent event.
Conclusions
The risk of stroke recurrence was substantial, especially after IS, but the risk varied among subgroups. The risk of mortality was higher after a recurrent than first-time stroke.
RISK PREDICTION OF 30-DAY MORTALITY AFTER STROKE USING STATISTICAL MODELS AND MACHINE LEARNING: A NATIONWIDE REGISTRY-BASED COHORT STUDY
Abstract
Background And Aims
We aimed to develop, validate and compare statistical and machine learning (ML) models for predicting the risk of 30-day mortality after hospital admission for stroke.
Methods
Data from the UK Sentinel Stroke National Audit Program from 2013 to 2019 were used. XGBoost, Logistic Regression (LR), LR with elastic net, and LR with elastic net and interaction term models were developed using 80% randomly selected 2013 to 2018 admissions, internally validated on the 20% remaining admissions, and temporally validated on all 2019 admissions. The models were developed with 30 variables chosen from expert advice and literature review. An LR reference model was developed with 4 variables. Performance of the risk prediction models was evaluated in terms of discrimination, calibration, reclassification, Brier scores, and Decision-curve analysis.
Results
Data from 488,497 patients were used, with an overall 30-day mortality of 12.3%. In the 2019 temporal validation set, XGBoost model obtained the lowest Brier score of 0.069 (95% CI: 0.068-0.071) and the highest AUC 0.895 (95% CI: 0.891-0.900). Adding more variables improved the accuracy of all models. The XGBoost model appropriately reclassified 1648 (8.1%) cases as being moderate or high risk which was deemed low risk by the LR reference model.
Conclusions
The potential gain for ML versus carefully developed statistical models to produce more accurate risk predictions of stroke mortality is likely to be modest. These findings emphasise the usefulness of collecting more detailed clinical data to support predictive analytics in stroke care.
THE ROLE OF SMOKING FOR SOCIAL INEQUALITY IN SURVIVAL AFTER STROKE
Abstract
Background And Aims
Low income associates with increased stroke mortality. Low-income people's higher smoking frequency is considered a major cause of the increased mortality. We investigated the significance of smoking for social inequality in mortality after stroke.
Methods
We studied the association between income (5 groups) and the risk of death after stroke by merging data on incident stroke from Danish registries with nationwide coverage. We identified all incident cases of stroke hospitalized in Denmark during the years 2003-2012 (n=60503) of which 20953 (34.6%) died during follow-up. Patients were followed up to 9 years after stroke (median 2.6 years). Adjusting for age and sex we studied all-cause death and stratified by income and smoking.
Results
Of the patients 18681 (30.9%) were never-smokers; 33265 (55.0%) were current/former-smokers; smoking-status was unknown in 8557 (14.1%). Differences in short-term mortality between income groups (one-month to one-year) were clinically insignificant. Long-term mortality rates were, however, inversely and significantly related to income. Difference in mortality between the lowest and highest income group at 5 years after stroke was: All patients 15.5/5.7% (relative/absolute); never-smokers 13.0/4.4 %; current/former-smokers 19.5/5.9%. Thus, social inequality prevails independent of smoking the latter explaining no more than 19% (13.0/15.5) of the relative difference in mortality between the highest and lowest income group.
Conclusions
Social inequality in stroke mortality is striking favoring the most affluent by 15.5% lower 5-year mortality. Smoking plays a role, however, modest explaining no more than 1/5 of the difference in mortality between low and high income patients.
MECHANICAL THROMBECTOMY FOR BASILAR ARTERY OCCLUSION STROKE: ANALYSIS OF THE GERMAN STROKE REGISTRY-ENDOVASCULAR TREATMENT (GSR-ET)
Abstract
Background And Aims
Stroke due to basilar artery occlusion (BAO) causes the most severe strokes with poor prognosis. Data regarding efficacy of mechanical thrombectomy (MT) in BAO are sparse.
Methods
Patients enrolled between 06/2015 and 12/2019 in the German Stroke Registry-Endovascular Treatment (GSR-ET) were analyzed. The GSR-ET is an independent, prospective, multicenter, observational registry with 25 participating stroke centers in Germany enrolling patients treated with MT. Primary outcomes were successful reperfusion (mTICI score of 2b-3), substantial neurological improvement (≥ 8 NIHSS reduction from admission to discharge or NIHSS at discharge ≤ 1), and good functional outcome at 3-months (modified Rankin Scale (mRS) of 0-2).
Results
640 (9.6%) of the 6635 patients in the GSR were BAO-strokes. The majority of patients were pre-stroke functionally independent (pmRS 0-2 78.2%) and suffered from severe strokes with a median NIHSS of 17 (IQR 8, 27). Successful reperfusion was observed in 86.6%. Substantial neurological improvement could be achieved in 45.5%. At 3 months follow-up, 25.8% of patients showed a good functional outcome, mortality was 32.5%. Analysis of TICI3 versus TICI2b showed considerable better outcomes at 3-months in TICI 3 (good outcome in 31.9% versus 19.3% p=0.005). Strongest predictor for good functional outcome were IVT-treatment (OR 3.04, 95% CI 1.76-5.23) and successful reperfusion (OR 4.92, 95% CI 1.15-21.11).
Conclusions
Acute reperfusion strategies of BAO are common in daily practice and can be performed safely. Our data suggest that IVT-treatment and successful reperfusion strongly predicts good outcome with TICI3 showing advantages over TICI2b.
Trial Registration Number
The study was conducted in accordance with the Declaration of Helsinki and was centrally approved by the Institutional Review Board of the Ludwig-Maximilians-Universität, Munich, Germany (protocol No. 689- 15).
DAY AND NIGHT IN ACUTE STROKE PREHOSPITAL TRIAGE: A POST-HOC ANALYSIS OF THE RACECAT TRIAL
Abstract
Background And Aims
We aim to assess whether time of day modified the treatment effect of the intervention in the RACECAT trial.
Methods
We performed a secondary analysis of RACECAT to evaluate if direct transfer to a thrombectomy-capable center, as compared to transfer to a local stroke center, influence on functional outcome differed according to treatment allocation time: daytime(8:00AM-8:59PM) and nighttime(9:00PM-7:59AM) in patients with ischemic stroke. Primary outcome was modified Rankin score at 90 days.
Results
Of the 1369 patients in the intention to treat population, 949 patients (67%) had an ischemic stroke (mean age 74 ±13 years; 428 women (45.1%); median RACE score 7 (IQR 6 to 8)); 258 of them (27%) were evaluated during nighttime. The odds of better disability outcomes differed according to time of day, favoring direct transfer to a thrombectomy-capable center during nighttime: adjusted common odds ratio (acOR) during daytime, 0.890 (95% confidence interval (CI) 0.680 to 1.163); acOR during nighttime, 1.620 (95% CI 1.020 to 2.551) (pinteraction=0.014). Subgroup analysis revealed a significant heterogeneity in the observed interaction across stroke subtypes; influence of nighttime on the intervention effect was only present in patients with large vessel occlusion: acOR during daytime, 0.766 (95% CI 0.548-1.072); acOR during nighttime, 1.785 (95% CI 1.024 to 3.112) (pinteraction=0.01).
Conclusions
In patients that are evaluated during nighttime for a suspected stroke with high odds of harboring a large vessel occlusion in areas not covered by thrombectomy-capable stroke centers, direct transfer to a thrombectomy-capable center is associated with lower degrees of disability at 3 months.
Trial Registration Number
NCT02795962