Abstract only Background: Patient engagement and knowledge translation are increasingly recognized as critical components of stroke research. However, it is unclear how these components are currently ...perceived by interested parties. Methods: The PERSPECT (Priorities and Expectations of Researchers, Donors, Patients, and the Public Regarding the Funding and Conduct of Stroke Research) qualitative study involved in-depth, semi-structured interviews with patients, members of the general public, researchers, and donors, including board members of funding organizations and philanthropists. Participants were asked to discuss their thoughts about the role of patient and public engagement in stroke research and on the translation/dissemination of research findings. Collected data were analyzed through constant comparison and theme identification, followed by grounded theory content analysis. Results: Forty-one interviews were completed (11 with researchers and 10 for each patients, public and donors). An important theme that emerged was a need to re-evaluate and broaden conventional definitions of “expertise” in the context of selecting grant application review panels, recognizing the value of lived experience alongside that of education and professional experience. Whereas participants identified an important role for patient voices in guiding research direction and design; concerns were raised about the limited public awareness and understanding of medical research, which may hinder meaningful, advantageous involvement in the research process, as well as trust in evidence-based recommendations. In this regard, lay participants highlighted media-driven misinformation and a lack of credible lay-language resources as impeding effective dissemination of research findings. Conclusions: All four participant groups recognized the importance of knowledge end-users being engaged in research from its early stages, including decision-making about funding allocation. Impactful involvement seems however hindered by knowledge and communication gaps between the research and lay communities. Our results underscore the importance of efforts to make ongoing research and study findings more visible, accessible, and comprehensible.
Patients with pre-morbid disability have been generally excluded from randomized controlled trials of mechanical thrombectomy for acute ischemic stroke. However, stroke physicians commonly encounter ...such patients in practice, and face challenging treatment decisions when caring for them.
We review the literature on the safety and efficacy of thrombectomy in patients with pre-morbid disability. Recent clinical-epidemiological studies have highlighted the adverse outcomes that come with each increment of additional post-stroke disability in these patients. Several observational studies - both case series and registry-based studies - have helped demonstrate the comparable safety of thrombectomy in patients with pre-morbid disability as in those without, complementing similar data on thrombolysis. These data also suggest similar rates of successful recanalization, symptomatic intracerebral hemorrhage, and return to pre-stroke level of disability when treated with mechanical thrombectomy, although they have higher mortality.
In the absence of high-quality evidence, we recommend pursuing shared decision-making with patients or family members and being upfront about the uncertain evidence. Available observational data underline the potential for a substantial proportion of these patients to return to their pre-morbid state, do not indicate a greater rate of treatment-related complications, and do not support routinely excluding these patients from thrombectomy.
Abstract only Introduction: Age is a predictor of functional outcome after acute ischemic stroke (AIS). Frailty increases with age and comorbidities, and imaging markers of brain-frailty (e.g. ...atrophy, small-vessel-disease) are associated with outcomes. However, the extent to which the association of age and 90-day outcome is mediated by brain-frailty is unknown. We explored this mediation in AIS patients receiving endovascular therapy (EVT), with a particular interest in neuroimaging. Methods: In this post-hoc analysis of the ESCAPE-NA1 trial, in which all patients underwent EVT, we assessed brain atrophy (subcortical/cortical), white-matter disease (periventricular/deep) and the number of lacunes and chronic infarctions. Structural equation modelling (SEM) was used to create 3 latent variables: “imaging-frailty” (above-mentioned markers), “clinical-frailty” (e.g. pre-stroke mRS, cardiovascular risk factors, cancer) and “total-frailty” (imaging + clinical markers). We created 3 models ( figure1) including each latent variable as a potential mediator of the association of age and 90-day outcome, adjusting for baseline ASPECTS, NIHSS, onset-to-puncture-time, nerinetide and alteplase. Results: Among 1,092 patients, the indirect effect of age on 90-day outcome, mediated by imaging-frailty, contributed 96% of the total effect(β=0.047;p=0.02), while the indirect effect through clinical-frailty accounted for only 21%(β=0.01;p=0.001) of the total effect. When including both frailty constructs, the indirect pathway accounted for 86% of the total effect(β=0.06;p<0.01). These proportions were similar when imaging features were assessed on MRI. Conclusions: Brian frailty mediates the association of age and 90-day outcome after EVT, with most of the effect mediated by imaging as opposed to clinical markers of frailty. This work underscores the importance of considering brain-frailty, as opposed to chronological age alone, in predicting post-stroke outcomes.
BACKGROUND AND OBJECTIVESBrain frailty may impair the ability of acute stroke patients to cope with the injury, irrespective of their chronologic age, resulting in impaired recovery. We aim to ...investigate the impact of brain atrophy on functional outcome assessed at different time points after endovascular thrombectomy (EVT).METHODSIn this retrospective post hoc analysis of the ESCAPE-NA1 trial, we analyzed CT imaging data for cortical atrophy by using the GCA scale, including region-specific scales, and subcortical atrophy by using the intercaudate distance to inner table width (CC/IT) ratio. The primary outcome was 90-day mRS (ordinal shift analysis), and the secondary outcome was the mRS score over time. Adjustments were made for age, sex, baseline NIHSS, final infarct volume, stroke laterality, total Fazekas score, and nerinetide-alteplase interaction. Sensitivity analyses were additionally performed in only those patients for whom MRI data were available.RESULTSOf 1,102 participants (mean age of 69.5 ± 13.7 years; 554 men), 818 (74%) had GCA = 0, 220 (20%) had GCA = 1, and 64 (6%) had GCA = 2/3. The median CC/IT ratio was 0.12 (IQR0.10-0.15). Cortical atrophy (GCA ≥ 1 vs GCA 0) was associated with worse 90-day mRS (acOR = 1.62 95% CI 1.22-2.16; p = 0.001), lower rates of 90-day mRS0-2 (aOR = 0.65 95% CI 0.45-0.94; p = 0.022), and higher mortality (aOR = 2.12 95% CI 1.28-3.5; p = 0.003), regardless of the region assessed. Subcortical atrophy was associated with worse 90-day mRS (acOR per 0.01 increase in CC/IT ratio = 1.07 95% CI 1.04-1.11; p < 0.001) and lower rates of 90-day mRS0-2 (aOR = 0.92 95% CI 0.88-0.97; p = 0.001). Furthermore, with various degrees of atrophy, we observed heterogeneity in mRS measurements during follow-up: worse mRS scores for higher atrophy grades (p < 0.001). Compared with participants with GCA = 0, the mRS for participants with GCA = 1 was higher at 30 days (adjusted difference = 0.41 95% CI 0.18-0.65) and remained worse at 90 days (adjusted difference = 0.72 95% CI 0.49-0.95). Similar effects were seen for participants with worse cortical atrophy, regardless of the region assessed, and worse subcortical atrophy. Furthermore, 26/63(41%) and 124/274(45%) patients with severe cortical/subcortical atrophy (GCA 2/3 and highest CC/IT ratio quartile, respectively) achieved good functional outcome (mRS0-2), compared with 539/812(66.4%) with no cortical atrophy and 209/274(76%) in the lowest CC/IT ratio quartile.DISCUSSIONIn this large RCT-derived population, participants with brain atrophy, as visually assessed on acute noncontrast computed tomography imaging, showed less favorable stroke recovery after EVT and worse 90-day functional outcomes compared with participants without brain atrophy. This may support physicians with recovery expectations when planning post-EVT care with patients and their families.
Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic ...attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke.
We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602.
Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years IQR 0·19–2·44) were included in our analyses. The adjusted hazard ratio aHR comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20–1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82–3·29) for intracranial haemorrhage and 1·23 (1·08–1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 95% CI 3·08–6·72 for intracranial haemorrhage vs 1·47 1·19–1·80 for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 3·36–9·05 vs 1·43 1·07–1·91; and for ≥20 cerebral microbleeds, aHR 8·61 4·69–15·81 vs 1·86 1·23–2·82). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes 95% CI 48–84 per 1000 patient-years vs 27 intracranial haemorrhages 17–41 per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes 46–108 per 1000 patient-years vs 39 intracranial haemorrhages 21–67 per 1000 patient-years).
In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden.
British Heart Foundation and UK Stroke Association.
Brain atrophy is an important surrogate for brain reserve, the capacity of the brain to cope with acquired injuries such as acute stroke. It is unclear how well atrophy measurements on MR imaging can ...be reproduced using NCCT imaging. We aimed to compare pragmatic atrophy measures on NCCT with MR imaging in patients with acute ischemic stroke.
This is a post hoc analysis, including baseline NCCT and 24-hour follow-up MR imaging data from the Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Cortical atrophy was measured using the global cortical atrophy scale, and subcortical atrophy was measured using the intercaudate distance-to-inner-table width (CC/IT) ratio. Agreement and correlation between these measures on NCCT and MR imaging were calculated using the Gwet agreement coefficient 1 and Pearson correlation coefficients, respectively.
Among 1105 participants in the ESCAPE-NA1 trial, interpretable NCCT and 24-hour MR imaging were available in 558 (50.5%) patients (mean age, 67.2 SD, 13.7 years; 282 women). Cortical atrophy assessments performed on NCCT underestimated atrophy severity compared with MR imaging (eg, patients with global cortical atrophy of ≥1 assessed on NCCT = 133/558 23.8% and on MR imaging = 247/558 44.3%; a 20.5% difference). Overall, cortical (ie, global cortical atrophy) atrophy assessments on NCCT had substantial or better agreement with MR imaging (Gwet agreement coefficient 1 of > 0.784;
< .001). Subcortical atrophy measures (CC/IT ratio) showed strong correlations between NCCT and MR imaging (Pearson correlation = 0.746,
< .001).
Brain atrophy can be evaluated using simple measures in emergently acquired NCCT. Subcortical atrophy assessments on NCCT show strong correlations with MR imaging. Although cortical atrophy assessments on NCCT are strongly correlated with MR imaging ratings, there is a general underestimation of atrophy severity on NCCT.
Treatment with endovascular therapy in the extended time window for acute ischaemic stroke with large vessel occlusion involves stringent selection criteria based on the two landmark studies DAWN and ...DEFUSE3. Current protocols typically include the requirement of advanced perfusion imaging which may exclude a substantial proportion of patients from receiving a potentially effective therapy. Efforts to offer endovascular reperfusion therapies to all appropriate candidates may be facilitated by the use of simplified imaging selection paradigms with widely available basic imaging techniques, such as non-contrast CT and CT angiography. Currently available evidence from our literature review suggests that patients meeting simplified imaging selection criteria may benefit as much as those patients selected using advanced imaging techniques (CT perfusion or MRI) from endovascular therapy in the extended time window. A comprehensive understanding of the role of imaging in patient selection is critical to optimising access to endovascular therapy in the extended time window and improving outcomes in acute stroke. This article provides an overview on current developments and future directions in this emerging area.
According to the Response Assessment in Neuro-Oncology criteria, new enhancement within the radiation field on contrast enhanced T1-weighted images within 12 weeks after completion of radiotherapy ...should not qualify for progressive disease, since up to 50% of these cases may be pseudoprogression (PsP). To validate this concept, we assessed incidence and overall survival (OS) of patients with suspected and confirmed PsP dependent on different time intervals and definitions of PsP.
Patients with newly diagnosed glioblastoma and an enhancement increase of at least 25% after completion of standard radiochemotherapy at month 1, 4, 7, or 10 were eligible. Based on the development of the enhancement in follow-up examinations, patients were categorized as either PsP (subgrouped as complete resolution/decrease >50% and decrease <50%/stable) or true progression.
Out of 548 patients, 79 fulfilled the inclusion criteria. Of these 79 patients, 9 (11.4%) showed PsP (6/45 patients at 1 month, 2/17 at 4 months, 1/9 at 7 months, and 0/8 at 10 months). Complete resolution of the enhancement was found in 1, decrease >50% in 3, decrease <50% in 2, and stable enhancement in 3 patients with PsP. Patients with PsP showed a significantly longer OS (P < .012). No difference in OS was found among PsP subgroups.
This series challenges the current concept of PsP. Even though we could confirm a prolonged OS of patients with PsP, the incidence of PsP was lower than reported previously and extended beyond 12 weeks.
OBJECTIVETo validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables.
METHODSIn ...this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization.
RESULTSOf 788 included patients, 783 completed their 90-day follow-up, and 118 patients (15%) died. After full adjustment, MR-proANP levels were associated with 90-day mortality (adjusted hazard ratio 6.12, 95% confidence interval CI 2.36–15.84, p = 0.01) and functional outcome (adjusted odds ratio aOR 2.46, 95% CI 1.05–5.74, p = 0.038). For mortality prediction, adding MR-proANP to the regression model increased its discriminatory accuracy, and the continuous net reclassification index (cNRI) was 49% (95% CI 26%–78%, p < 0.001). For functional outcome, there was no significant improvement in discrimination or reclassification. Cardioembolic stroke etiology and the diagnosis of atrial fibrillation at hospital discharge were associated with MR-proANP with an aOR of 2.10 (95% CI 1.11–3.97, p = 0.02) and 18.35 (95% CI 7.94–42.45, p < 0.001), respectively. The cNRI of MR-proANP for cardioembolic stroke etiology was not significant, as opposed to atrial fibrillation (78%, 95% CI 60%–89%, p < 0.001). MR-proANP levels ≥289 pmol/L had a specificity of 86% and sensitivity of 48% for the diagnosis of atrial fibrillation.
CONCLUSIONMR-proANP is a newly validated blood biomarker providing additional prognostic information for mortality after stroke. Higher MR-proANP levels were associated with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.
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