Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.

PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke. METHODS: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease. RESULTS: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke. CONCLUSION: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship.

Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.

BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. PATIENTS AND METHODS: MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. RESULTS: Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). CONCLUSION: Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.

IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke.

BACKGROUND OBJECTIVES: It is unclear whether IV thrombolysis (IVT) outperforms early dual antiplatelet therapy (DAPT) in the acute setting of mild ischemic stroke. The aim of this study was to compare the early safety and efficacy of IVT with that of DAPT. METHODS: Data of mild noncardioembolic stroke patients with admission NIH Stroke Scale (NIHSS) score ≤3 who received IVT or early DAPT in the period 2018-2021 were extracted from a nationwide, prospective stroke unit registry. Study endpoints included symptomatic intracerebral hemorrhage (sICH), early neurologic deterioration ≥4 NIHSS points (END), and 3-month functional outcome by modified Rankin scale (mRS). RESULTS: A total of 1,195 mild stroke patients treated with IVT and 2,625 patients treated with DAPT were included. IVT patients were younger (68.1 vs 70.8 years), had less hypertension (72.8% vs 83.5%), diabetes (19% vs 28.8%), and a history of myocardial infarction (7.6% vs 9.2%), and slightly higher admission NIHSS scores (median 2 vs median 1) when compared with DAPT patients. After propensity score matching and multivariable adjustment, IVT was associated with sICH (4 [1.2%] vs 0) and END (adjusted odds ratio [aOR] 2.8, 95% CI 1.1-7.5), and there was no difference in mRS 0-1 at 3 months (aOR 1.3, 95% CI 0.7-2.6). DISCUSSION: This analysis from a prospective nationwide stroke unit network indicates that IVT is not superior to DAPT in the setting of mild noncardioembolic stroke and may eventually be associated with harm. Further research focusing on acute therapy of mild stroke is highly warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT is not superior to DAPT in patients with acute mild (NIHSS score ≤3) noncardioembolic stroke. The study lacks the statistical precision to exclude clinically important superiority of either therapy.

Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial.

BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. METHODS: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2-20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. RESULTS: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2-12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57-0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48-3.13]). CONCLUSIONS: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02930018.

Temporal Trends of Functional Outcome in Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis.

BACKGROUND: Intravenous thrombolysis improves functional outcome in patients with acute stroke and frequencies of r-tPA (recombinant tissue-type plasminogen activator) treatment have been increasing over time. We aimed to assess whether functional outcome in r-tPA-treated patients improved over time and to investigate the influence of clinical variables on functional outcome. METHODS: We analyzed data of r-tPA-treated patients in the Austrian Stroke Unit Registry from 2006 to 2019. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 2. Frequencies of modified Rankin Scale score of 0 to 2 were assessed for the overall population and in prespecified subgroups; multivariable logistic regression analysis was performed to assess associations of baseline characteristics including clinically relevant interactions, and outcome. RESULTS: Overall, 4865 out of 9409 r-tPA-treated patients (51.7%) achieved favorable functional outcome 3 months post stroke. Between 2006 and 2019, frequencies of favorable functional outcome increased from 45.9% to 56.8%. In multivariable logistic regression analysis, year of treatment (adjusted odds ratio [adjOR], 1.08 [95% CI, 1.01-1.15]) was associated with favorable functional outcome. Stroke severity (National Institutes of Health Stroke Scale, adjOR, 0.86 [95% CI, 0.85-0.87]), age (61-70 years: adjOR, 0.67 [95% CI, 0.55-0.80], 71-80 years: adjOR, 0.42 [95% CI, 0.35-0.50], >80 years: adjOR, 0.16 [95% CI, 0.13-0.20]), female sex (adjOR, 0.89 [95% CI, 0.79-0.99]), and various comorbidities (eg, atrial fibrillation, prior stroke, diabetes) were negatively associated. Inclusion of interaction terms into the multivariable logistic regression model suggests a positive effect of year of treatment and endovascular treatment by increasing stroke severity on functional outcome (interaction between year of treatment and National Institutes of Health Stroke Scale: adjOR, 1.01 [95% CI, 1.00-1.02], interaction between National Institutes of Health Stroke Scale and endovascular treatment: adjOR, 1.02 [95% CI, 1.01-1.03]). CONCLUSIONS: Frequencies of favorable functional outcome in r-tPA-treated patients have been increasing over time, likely driven by improved outcome in patients with more severe strokes receiving endovascular treatment. However, some subgroups are still less likely to achieve functional independency and deserve particular attention.

Association of Stent-Retriever Characteristics in Establishing Successful Reperfusion During Mechanical Thrombectomy : Results from the ESCAPE-NA1 Trial.

BACKGROUND: Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial. METHODS: Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built. RESULTS: Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46). CONCLUSION: The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Thrombectomy in basilar artery occlusion.

BACKGROUND AND PURPOSE: The benefit of thrombectomy (TE) for acute ischemic stroke (AIS) in patients suffering basilar artery occlusion (BAO) is still unclear. Our aim was to analyze functional outcome after 3 months in BAO compared to anterior circulation large vessel occlusion (ACLVO) in a nationwide registry. METHODS: Patients enrolled into the Austrian Endostroke Registry from 2013 to 2018 were analyzed. We used propensity score matching to control for imbalances and to compare patients with BAO and ACLVO. The primary outcome was favorable functional outcome after 3 months measured by the modified Rankin Scale (mRS) (0-2). Multivariate models were applied to estimate the effect of localization (BAO vs ACLVO). RESULTS: In total, 2288 patients underwent TE for AIS with proximal vessel occlusion, of these 267 with BAO. Two hundred and sixty-four patients with BAO were matched to 264 patients with ACLVO. Baseline characteristics were well-balanced. The 90-day mortality did not significantly differ between patients with BAO and ACLVO. In a multivariate logistic regression model, we did not detect a significant difference in functional outcome between BAO and ACLVO (odds ratio for favorable outcome defined as mRS = 0-2: 1.19; 95% confidence interval (CI) = 0.78-1.81; p = 0.42). In patients with an onset-to-door-time ⩾270 min, TE of BAO was associated with poor functional outcome defined as mRS 3-6 (odds ratio (OR) = 3.97; 95% CI = 1.32-11.94; p = 0.01) as compared to ACLVO. CONCLUSION: In this study, functional outcome did not differ after TE in patients with BAO and ACLVO overall; however, we detected an association of BAO with poor outcome in patients arriving late.

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.

BACKGROUND: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial. METHODS: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling. RESULTS: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1). CONCLUSIONS: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Variability assessment of manual segmentations of ischemic lesion volume on 24-h non-contrast CT.

PURPOSE: Infarct lesion volume (ILV) may serve as an imaging biomarker for clinical outcomes in the early post-treatment stage in patients with acute ischemic stroke. The aim of this study was to evaluate the inter- and intra-rater reliability of manual segmentation of ILV on follow-up non-contrast CT (NCCT) scans. METHODS: Fifty patients from the Prove-IT study were randomly selected for this analysis. Three raters manually segmented ILV on 24-h NCCT scans, slice by slice, three times. The reference standard for ILV was generated by the Simultaneous Truth And Performance Level estimation (STAPLE) algorithm. Intra- and inter-rater reliability was evaluated, using metrics of intraclass correlation coefficient (ICC) regarding lesion volume and the Dice similarity coefficient (DSC). RESULTS: Median age of the 50 subjects included was 74.5 years (interquartile range [IQR] 67-80), 54% were women, median baseline National Institutes of Health Stroke Scale was 18 (IQR 11-22), median baseline ASPECTS was 9 (IQR 6-10). The mean reference standard ILV was 92.5 ml (standard deviation (SD) ± 100.9 ml). The manually segmented ILV ranged from 88.2 ± 91.5 to 135.5 ± 119.9 ml (means referring to the variation between readers, SD within readers). Inter-rater ICC was 0.83 (95%CI: 0.76-0.88); intra-rater ICC ranged from 0.85 (95%CI: 0.72-0.92) to 0.95 (95%CI: 0.91-0.97). The mean DSC among the three readers ranged from 65.5 ± 22.9 to 76.4 ± 17.1% and the mean overall DSC was 72.8 ± 23.0%. CONCLUSION: Manual ILV measurements on follow-up CT scans are reliable to measure the radiological outcome despite some variability.

From Three-Months to Five-Years: Sustaining Long-Term Benefits of Endovascular Therapy for Ischemic Stroke.

Background and Purpose: During the months and years post-stroke, treatment benefits from endovascular therapy (EVT) may be magnified by disability-related differences in morbidity/mortality or may be eroded by recurrent strokes and non-stroke-related disability/mortality. Understanding the extent to which EVT benefits may be sustained at 5 years, and the factors influencing this outcome, may help us better promote the sustenance of EVT benefits until 5 years post-stroke and beyond. Methods: In this review, undertaken 5 years after EVT became the standard of care, we searched PubMed and EMBASE to examine the current state of the literature on 5-year post-stroke outcomes, with particular attention to modifiable factors that influence outcomes between 3 months and 5 years post-EVT. Results: Prospective cohorts and follow-up data from EVT trials indicate that 3-month EVT benefits will likely translate into lower 5-year disability, mortality, institutionalization, and care costs and higher quality of life. However, these group-level data by no means guarantee maintenance of 3-month benefits for individual patients. We identify factors and associated "action items" for stroke teams/systems at three specific levels (medical care, individual psychosocioeconomic, and larger societal/environmental levels) that influence the long-term EVT outcome of a patient. Medical action items include optimizing stroke rehabilitation, clinical follow-up, secondary stroke prevention, infection prevention/control, and post-stroke depression care. Psychosocioeconomic aspects include addressing access to primary care, specialist clinics, and rehabilitation; affordability of healthy lifestyle choices and preventative therapies; and optimization of family/social support and return-to-work options. High-level societal efforts include improving accessibility of public/private spaces and transportation, empowering/engaging persons with disability in society, and investing in treatments/technologies to mitigate consequences of post-stroke disability. Conclusions: In the longtime horizon from 3 months to 5 years, several factors in the medical and societal spheres could negate EVT benefits. However, many factors can be leveraged to preserve or magnify treatment benefits, with opportunities to share responsibility with widening circles of care around the patient.

A Detailed Analysis of Infarct Patterns and Volumes at 24-hour Noncontrast CT and Diffusion-weighted MRI in Acute Ischemic Stroke Due to Large Vessel Occlusion: Results from the ESCAPE-NA1 Trial.

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

Rethinking Consent for Stroke Trials in Time-Sensitive Situations: Insights From the COVID-19 Pandemic.

Informed consent is a key concept to ensure patient autonomy in clinical trials and routine care. The coronavirus disease 2019 (COVID-19) pandemic has complicated informed consent processes, due to physical distancing precautions and increased physician workload. As such, obtaining timely and adequate patient consent has become a bottleneck for many clinical trials. However, this challenging situation might also present an opportunity to rethink and reappraise our approach to consent in clinical trials. This viewpoint discusses the challenges related to informed consent during the COVID-19 pandemic, whether it could be acceptable to alter current consent processes under these circumstances, and outlines a possible framework with predefined criteria and a system of checks and balances that could allow for alterations of existing consent processes to maximize patient benefit under exceptional circumstances such as the COVID-19 pandemic without undermining patient autonomy.

Distributed changes of the functional connectome in patients with glioblastoma.

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.

Prevalence of Non-Stenotic (<50%) Carotid Plaques in Acute Ischemic Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

INTRODUCTION: Non-stenotic (<50%) carotid plaques have recently been recognized as a potential source of stroke. This meta-analysis aims to summarize the prevalence of non-stenotic carotid plaques in stroke patients in general and in patients with embolic stroke of undetermined source in particular. METHODS: We performed a comprehensive systematic review of the literature and meta-analysis on acute ischemic stroke patients in whom carotid imaging was performed using the MEDLINE, Embase and Cochrane database, including studies published up to December 2019. Keywords were "stroke", "transient ischemic attack", "carotid", "plaque", "atherosclerosis" and "disease". Included studies had ≥10 patients with acute ischemic stroke and reported the prevalence of non-stenotic (<50%%stenosis) carotid plaques detected on any imaging modality. RESULTS: We included forty-five studies (n = 18304 patients, 48.4% males, mean age 63.6 years) in our meta-analysis. Imaging modalities used were ultrasound (n = 26 studies), CT-angiography (n = 7), magnetic resonance-imaging (n = 8) and catheter angiography (n = 4). The overall prevalence of non-stenotic carotid plaques was 51% (95% CI: 43 - 59). 10 studies included mainly patients with embolic stroke of undetermined source (>50% of all patients). The pooled prevalence of non-stenotic carotid plaques in these studies was 55% (95% CI: 42 - 68). 23 studies explicitly reported ipsilateral non-stenotic carotid plaques, the pooled prevalence of which was 51% (95% CI: 45 - 59). CONCLUSIONS: In this meta-analysis, non-stenotic carotid plaques were present in more than 50% of all acute ischemic stroke patients, with a slightly higher prevalence in ESUS patients. Given the potential role of non-stenotic carotid plaques in stroke etiology, particularly in ESUS, further research should aim to identify criteria that predict the stroke risk associated with non-stenotic carotid plaques.

Prevalence and Outcomes of Medium Vessel Occlusions With Discrepant Infarct Patterns.

BACKGROUND AND PURPOSE: The prognosis of medium vessel occlusions (MeVOs), that is, M2/3 middle cerebral artery, A2/3 anterior cerebral artery, and P2/3 posterior cerebral artery occlusions, is generally better compared with large vessel occlusions, since brain ischemia is less extensive. However, in some MeVO patients, infarcts are seen outside the territory of the occluded vessel (MeVO with discrepant infarcts). This study aims to determine the prevalence and clinical impact of discrepant infarct patterns in acute ischemic stroke due to MeVO. METHODS: We pooled data of MeVO patients from INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRove-IT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy)-2 prospective cohort studies of patients with acute ischemic stroke. The combination of occlusion location on baseline computed tomography angiography and infarct location on follow-up computed tomography/magnetic resonance imaging was used to identify MeVOs with discrepant infarct patterns. Two definitions for discrepant infarcts were applied; one was more restrictive and purely based on infarct patterns of the basal ganglia, whereas the second one took cortical infarct patterns into account. Clinical outcomes of patients with versus without discrepant infarcts were summarized using descriptive statistics. Logistic regression was performed to obtain adjusted effect size estimates for the association of discrepant infarcts and good outcome, defined as a modified Rankin Scale score of 0 to 2, and excellent outcome (modified Rankin Scale score 0-1). RESULTS: Two hundred sixty-two patients with MeVO were included in the analysis. The prevalence of discrepant infarcts was 39.7% (definition 1) and 21.0% (definition 2). Patients with discrepant infarcts were less likely to achieve good outcome (definition 1: adjusted odds ratio, 0.48 [95% CI, 0.25-0.91]; definition 2: adjusted odds ratio, 0.47 [95% CI, 0.22-0.99]). When definition 1 was applied, patients with discrepant infarcts were also less likely to achieve excellent outcome (definition 1: adjusted odds ratio, 0.55 [95% CI, 0.31-0.99]; definition 2: adjusted odds ratio, 0.62 [95% CI, 0.31-1.25]). CONCLUSIONS: MeVO patients with discrepant infarcts are common, and they are associated with more severe deficits and poor outcomes.