Welcome to the WSC 2021 Interactive Program

Background and Aims

Radiological markers for cerebral small vessel disease (SVD) may have different biological underpinnings in their pathophysiology. However, there is no effective tool to individually categorize SVD. The relationships between white matter signal abnormalities (WMSA) features, lacunes, cerebral microbleeds (CMB) and enlarged perivascular space (EPVS) were quantified to categorize the phenotypes of SVD.

Methods

Data were acquired from healthy individuals who underwent comprehensive brain examinations for a health check-up program at a tertiary center. Among 647 individuals, 611 aged > 40 years were included after excluding 36 with minimal WMSA volume. The WMSA, lacunes, CMB and EPVS were quantified automatically or manually. The WMSA were classified by the number and size of non-contiguous lesions, distribution, and contrast. An algorithm with WMSA class and its interaction with other SVD markers was constructed to categorize individuals into distinct ‘types’ of SVD. Clinical and laboratory variability were determined across the individual SVD types.

Results

Type A was characterized by multiple, small, deep WMSA but a low burden of lacunes and deep CMB; Type B had large periventricular WMSA and a high burden of lacunes and deep CMB; and Type C had restricted juxtaventricular WMSA and lacked lacunes and deep CMB. Type B was associated with an older age and a higher prevalence of hypertension and diabetes. Smoking and high uric acid levels were associated with an increased risk of type A.

Conclusions

The heterogeneity of SVD was categorized into three types with distinct clinical correlates. This new categorization will improve our understanding of SVD pathophysiology, risk stratification and outcome prediction.

Background and Aims

Lipid-lowering medications (LLMs) are recommended for secondary prevention of stroke. Little is known about the association between their ongoing use post-discharge and outcomes. We investigated the use and adherence to LLMs within the first 90 days post-discharge for ischaemic stroke and associated 12-month outcomes.

Methods

Retrospective cohort study of 90-day survivors of ischaemic stroke from hospitals (n=45) in two Australian states participating in the Australian Stroke Clinical Registry (2012-2016). Person-level data were linked with Pharmaceutical Benefits Scheme (PBS), hospital and death datasets. LLM use within 90 days post-discharge was determined from PBS dispensing records. Among users, adherence was assessed using the proportion of days covered (PDC: <80% vs. ≥80%) within 90 days post-discharge. Outcomes during the subsequent year (91-455 days) included all-cause mortality and hospital readmissions (cardiovascular disease, all-cause). Associations between use/adherence and outcomes were determined using propensity score adjusted-multivariable Cox regression models.

Results

Of 11,217 eligible patients (median age 72 years, 42% female), 9,294 (83%) used LLMs within 90 days post-discharge, including 5,938 (64%) with PDC ≥80%. Compared to users, non-users, had greater rates of mortality [hazard ratio (HR) 2.35, 95% CI 1.89-2.93] or all-cause readmissions (HR 1.16, CI 1.09-1.22). Among users, those with PDC <80% had greater rates of mortality (HR 1.31, CI 1.14-1.51) or all-cause readmissions (HR 1.05, CI 1.00-1.09) than those with PDC ≥80%. There were no associations between use/adherence and cardiovascular disease readmissions.

Conclusions

Use and greater adherence to LLMs (90-days) for ischaemic stroke is associated with reduced all-cause mortality and readmissions.

Background and Aims

Vascular calcifications are considered to be part of active atherosclerosis. Coronary calcification have long become a prognostic marker. Calcifications of intracranial vessels(ICC) are frequently observed on non-contrast CT and their effect on post-stroke cognitive impairment(PSCI) remains unclear. Our aim was to explore the association of ICC with long-term cognitive and advanced MRI measures in a large prospective cohort of mild stroke/transient ischemic attack(TIA) patients

Methods

Data from the Tel Aviv brain acute stroke cohort(TABASCO) was analyzed. This prospective cohort study(n=575)aimed to identify predictors of PSCI. The ICC score(ICCS) on initial NCCT was calculated using a calcium quantification application. Participants underwent a 3T-MRI and comprehensive cognitive assessments at enrollment, 6, 12 and 24 months thereafter

Results

Baseline data were available for 531 subjects(mean age 67.4 years,59.5% males). The incidence of cognitive impairment at the two-year time mark was doubled in the high ICCS group(26% vs.13.7%,p<0.001).On multiple regression analysis higher ICCS was associated with brain atrophy manifested by lower normalized white matter(WM), gray matter(GM), hippocampal and thalamic volumes(β=-0.178,β=-0.200,β=-0.137,β=-0.157;p<0.05)and with lower cognitive scores at baseline,6- and 12-month post-stroke (β-0.14,β=-0.12, β=-0.12,respectively;p<0.05). Microstructural damage, defined by DTI analysis of the normal appearing white matter(NAWM), as well as all small vessel disease(SVD) markers were significantly increased in the high ICCS group(p<0.001, p=0.002, respectively).

Conclusions

Our findings suggest that the ICCS correlates with brain atrophy, the extent of SVD and long-term PSCI. This score, which is a readily available imaging marker, can assist in post-stroke prognostication and help provide individually tailored therapy by adjusting treatment targets in stroke survivors.

Background and Aims

Intravenous thrombolysis (IVT) can reduce disability after acute ischaemic stroke. The IVT rate in the UK (as a percentage of all strokes) has remained stable at 11-12% over the past 7 years.

Methods

Data from January 2019-December 2020 were extracted from the Sentinel Stroke National Audit Programme (SSNAP), a national registry covering 92% of the UK population. For all stroke admissions, we compared the annual and monthly IVT rates at national and regional level. Chi-squared was used to test the differences between cohorts.

Results

174,321 stroke patients were admitted to acute hospitals over two years. The national IVT rate decreased from 11.6% in 2019 to 11% in 2020, p<0.001. During the first UK COVID peak in March/April 2020, the IVT rate remained stable (11.6% in 2019 compared to 11.8% in 2020, p=0.652). However, IVT rates began to fall after April 2020, with a pronounced decline from autumn onwards (10.2% in September-December 2020 compared to 11.6% in September-December 2019, p<0.001).

Conclusions

Data shows that whilst the IVT rate was maintained during the early months of the pandemic (March-April 2020), rates began to decline through mid to late 2020. Further investigation is required to determine the underlying cause(s), which may include admission rates, organisational changes and increases in pre-hospital and in-hospital pathway timings, as well as to explore regional differences, as the pandemic affected different UK regions at different intensities.

Background and Aims

A significant proportion of the burden of non-communicable disease in adults has its roots in adolescence and this is particularly true for cardiovascular disease and stroke. Detection of risk factors, early stages of disease and laboratory abnormalities at young ages may aid disease prevention and management.

Methods

We systematically assessed the frequency of yet unknown medical conditions that require further diagnostic work-up or intervention (life-style counselling or pharmacotherapy) in 2088 adolescents sampled from the general population considering previously diagnosed physician-confirmed diseases. The easy-to-administer health screening included medical history taking, fasting blood analysis, and blood pressure and body measurements, and was performed at schools.

Results

Adolescents were on average 16.4 (SD 1.1) years old and 56.4 percent were female. The health screening newly detected relevant medical conditions in 45.4 [95% CI, 43.3–47.6] percent (55.8 [95% CI, 52.5–59.0] percent in boys and 37.4 [95% CI, 34.6–40.2] percent in girls). The most prevalent previously unknown medical conditions were vascular risk factors like elevated blood pressure (16.7%) and hypertension (10.2%), metabolic syndrome (3.0%), hypercholesterolemia (7.6%) and hypertriglyceridemia (9.6%). On the other hand, impaired fasting glucose and pre-diabetes were rare in this community-based sample of adolescents as were endocrine and other abnormalities (all <1.0%) except for subclinical hypothyroidism (5.7%) and hyperuricemia (7.8%).

Conclusions

Health screening in adolescence has a high diagnostic yield for previously unknown vascular risk factors, is feasible in the school setting, and may provide an opportunity for guideline-recommended targeted prevention in the young.

Background and Aims

The risk of haematoma expansion in intracerebral haemorrhage (ICH) increases with larger baseline volume until haemostasis or a tamponade is effected by the rigid cranium. We explored the association of ICH volume to intracranial volume ratio (ICH/ICV) with mass effect and whether it could predict haematoma expansion at 24-hour.

Methods

CT scans of 133 patients with ICH in the RIGHT-2 trial were analysed. ICH/ICV ratio (%) was estimated using semi-automated segmentation methods. Significant mass effect was defined as midline shift of ≥5mm or ambient cistern score of ≥1 (effacement of at least one ambient cistern). Multivariable logistic regression with adjustment for baseline variables was performed to explore the predictors of haematoma expansion (>6mL or >33%) and significant mass effect.

Results

The mean baseline ICH volume was 37.8 (38.6) mL and mean ICH/ICV ratio 2.68 (2.72)%. ICH/ICV ratio of ≥6% was significantly associated with ambient cistern effacement (adjusted odd ratio [aOR] 21.6, 95%CI 5.5-84.8) and midline shift ≥5mm (aOR 220) on baseline CT but not at lower cut-offs. Increasing ICH/ICV ratio predicted haematoma expansion but the effect plateaued at 3-4% when further increase did not significantly increase the aOR (Figure 1). The accuracy of ICH/ICV ratio in predicting haematoma expansion was similar compared to ICH volume (area under the receiver operator characteristics curve 0.69 for both, Figure 2).

Conclusions

ICH/ICV ratio predicted haematoma expansion and may be used to prognosticate or stratify patients in stroke trials testing potential treatments. The potential mechanisms and effect on functional outcomes need further exploration.

Background and Aims

Thrombus perviousness and length are important thrombus imaging characteristics related to outcome in patients with anterior circulation ischemic stroke. We investigated the association of thrombus characteristics with reperfusion and functional outcome in patients with posterior circulation stroke (PCS) who underwent endovascular treatment (EVT).

Methods

Thrombus imaging characteristics (perviousness, density, and length) were measured in patients with PCS registered in the MR CLEAN Registry between 2014-2018. All characteristics were assessed on thin-slice (<2.5mm) non-contrast computed tomography and computed tomography angiography imaging acquired within 30 minutes from each other. We compared thrombus characteristics in patients with or without excellent reperfusion (expanded Treatment In Cerebral Ischemia (eTICI) score ≥2C) and with or without favorable functional outcome (modified Rankin Scale score (mRS) 0-3) using the Mann-Whitney U-test.

Results

Sixty-six patients were analyzed. Median thrombus perviousness was 7 (IQR -1-21) Hounsfield Units (HU). Median density was 54 (IQR 44-66) HU and median length was 24 (IQR 15-42) mm. No significant between-group differences were found in thrombus characteristics (Table 1).

Conclusions

In this study of patients with PCS treated with EVT, thrombus imaging characteristics were not associated with reperfusion or functional outcome.

Background and Aims

The association of thrombus density with reperfusion and functional outcome remains conflicted in acute ischemic stroke. We evaluated if hyperdense thrombi were associated with reperfusion and functional outcome after endovascular treatment (EVT).

Methods

Thrombus imaging characteristics were measured in patients with M1 occlusions included in the MR CLEAN Registry. Thrombus density was measured on thin-slice (<2.5 mm) non-contrast computed tomography. Based on median density across the dataset, hyperdense thrombi were defined as thrombi >50 Hounsfield Units (HU). Regression models were used to investigate the association between hyperdense thrombi, successful reperfusion (expanded Treatment In Cerebral Ischemia (eTICI) score 2B-3), and favorable and excellent functional outcome (modified Rankin Scale (mRS) of 0-2 and 0-1, respectively) at 90 days. We adjusted for age, gender, baseline National Institutes of Health Stroke Scale, prestroke mRS, clot burden score, intravenous alteplase treatment (IVT) and carotid tandem lesions. Subgroup analyses were performed in patients treated with or without IVT prior to EVT.

Results

In 434 analyzed patients, hyperdense thrombi were not associated with successful reperfusion (aOR 0.99 [95%CI 0.65-1.51]) or favorable functional outcome (aOR 1.28 [95%CI 0.81-2.01]). Hyperdense thrombi were inversely associated with excellent functional outcome (aOR 0.52 [95%CI 0.32-0.85]). This association was stronger in patients treated with IVT prior to EVT (aOR 0.47 [95%CI 0.26-0.85]) than in EVT only patients (aOR 0.85 [95%CI 0.29-2.52]) (Figure 1).

Conclusions

Hyperdense thrombi were not significantly associated with reperfusion or favorable functional outcome. However, patients with hyperdense thrombi less often achieved excellent functional outcome after EVT.

Background and Aims

In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack (TIA) in the THALES trial, combination of ticagrelor and aspirin for 30 days reduced stroke or death but increased risk of severe bleeding in comparison to aspirin alone. We investigated the short-term time course for benefit and risk of ticagrelor-aspirin in these patients.

Methods

We evaluated the cumulative incidence of efficacy and safety of treatment for varying timepoints during 30-day follow-up. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or non-hemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage or fatal bleedings. Net clinical impact was defined as the combination of these two endpoints.

Results

The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction [ARR] 1.15%, 95% CI 0.36% to 1.94%), and remained throughout the 30-day treatment period. An increase of major hemorrhage was seen during the first week which remained relatively constant in the following weeks (absolute risk increase, approximately 0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (ARR 0.97%, 95% CI, 0.17% to 1.77%) and remained constant throughout the 30 days.

Conclusions

In patients with mild-moderate ischemic stroke or high-risk TIA, net clinical benefit was seen in the first week and remained during the entire 30-day study period. This analysis supports 30 days of dual antiplatelet therapy with ticagrelor and aspirin in these patients.

TRIAL REGISTRATION

clinicaltrials.gov Identifiers: NCT03354429

Background and Aims

Currently, it is unclear whether during endovascular treatment (EVT) for acute ischemic stroke, an extra pass should be undertaken to achieve more complete reperfusion after expanded Treatment In Cerebral Ischemia (eTICI) 2B is already achieved. We aimed to compare outcomes of single-pass good reperfusion (eTICI 2B) with multi-pass (near-)complete reperfusion (eTICI 2C-3) in daily clinical practice.

Methods

We included MR CLEAN Registry patients with M1 occlusions in whom EVT was ended either after achieving eTICI 2B in a single pass or after achieving eTICI 2C/3 in multiple passes. Regression models were used to investigate the association between single-pass eTICI 2B versus multi-pass eTICI 2C/3 with 24-hour National Institutes of Health Stroke Scale (NIHSS) score and 90-day functional outcome (modified Rankin Scale [mRS]).

Results

In 114 (28%) patients, eTICI 2B was achieved after a single pass; in 292 (72%) patients eTICI2C/3 was achieved after multiple passes. Patients with single-pass eTICI 2B showed lower 24-hour NIHSS scores (-19% [95% CI -33 to -1%]) and better functional outcomes (acOR 1.32 [95 % CI 0.93-1.87]) than patients with eTICI 2C/3 after ≥3 passes (Figure 1). No significant difference in functional outcomes was found between single-pass eTICI 2B and eTICI 2C/3 in two passes.

Conclusions

Our results do not provide arguments to continue an EVT procedure when eTICI 2B is reached after one pass, but further research is necessary to investigate the per-pass effect in relation to reperfusion and functional outcome.

Background and Aims

Previous studies indicate that patients with wake-up stroke (WUS) are similar to patients with known onset stroke (KOS), but may differ from patients with unknown-onset stroke (UOS). We compared risk factors and clinical characteristics in patients with ischemic WUS, UOS, and KOS from a large national stroke register.

Methods

We included patients registered in the Norwegian Stroke Register from 2012 to 2019. Information on age, gender, risk factors, medication and clinical characteristics were compared between patients with ischemic WUS, UOS and KOS.

Results

Of the 52 134 ischemic strokes, 19.8 % were WUS and 17.7% UOS. Patients with UOS were older (76.6 years, SD 12.6) than patients with WUS (73.6, SD 13.0) and KOS (73.5, SD 13.5). A higher proportion were women (50.3% vs. 43.0% in WUS and 44.8% in KOS) and lived alone (52.5% in the OUS group vs. 36.6% in both WUS and KOS groups). After adjustment for age and sex, atrial fibrillation was more frequent among UOS patients. Other cerebrovascular risk factors did not substantially differ between groups. WUS patients had milder strokes compared to UOS and KOS, while more UOS patients had NIHSS > 15 and reduced level of consciousness on admission.

Conclusions

WUS patients shared baseline characteristics with KOS, but tended to have milder strokes. UOS patients were older and larger proportions were women, lived alone, had atrial fibrillation and severe strokes compared to WUS and KOS patients. The results indicate that WUS and UOS should be considered separate entities.

Background and Aims

High-intensity statins are recommended as tertiary prevention after ischemic stroke, but evidence on different statin intensities and the risk of recurrence remains inconclusive. We examined the association between statin intensity and the risk of recurrent ischemic stroke.

Methods

In this Danish nationwide, population-based, new-user, active comparator cohort study, we used the Danish Stroke Registry to identify patients with a first-time ischemic stroke during 2004-2018. Patients who redeemed a statin prescription within 7 days after discharge were assigned to cohorts according to international guidelines on statin intensity. We used competing risk methods to compute 10-year risk differences (RDs) and Cox regression to compute adjusted hazard ratios (aHRs) of ischemic stroke recurrence and all-cause mortality, adjusting for age, sex, calendar period, stroke severity, and other risk factors.

Results

Low (n=305), moderate (n=29,325), and high (n=6,115) intensity statin users were followed for a median of 4.2 years. The risk of recurrence was largely similar among high-intensity users compared with moderate-intensity (RD: -0.3% [95% CI: -3.7; 3.0], aHR: 1.09 [95% CI: 0.95; 1.24]) and low-intensity users (RD: -2.8% [95% CI: -6.2; 0.6], aHR: 0.78 [95% CI: 0.56; 1.08]). The risk of all-cause mortality was lower among high-intensity users compared with low-intensity (RD: -21.8% [95% CI: -26.5; -17.0], aHR: 0.65 [95% CI: 0.53; 0.79]) and moderate-intensity users (RD: -12.4% [95% CI: -17.1; -7.6], aHR: 0.79 [95% CI: 0.71; 0.87]).

Conclusions

High-intensity statin use was not associated with a reduced risk of recurrent ischemic stroke. All-cause mortality was lowered in a possible dose-dependent manner.