Late Window Research Articles

Specialist Perspectives on the Imaging Selection of Large Vessel Occlusion in the Late Window.

The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window. We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others. Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001). Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging.

CT Perfusion vs Noncontrast CT for Late Window Stroke Thrombectomy: A Systematic Review and Meta-analysis.

Patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) in the late window (6-24 hours) can be evaluated with CT perfusion (CTP) or with noncontrast CT (NCCT) only. Whether outcomes differ depending on the type of imaging selection is unknown. We conducted a systematic review and meta-analysis comparing outcomes between CTP and NCCT for EVT selection in the late therapeutic window. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A systematic literature review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed databases. Studies focusing on late-window AIS undergoing EVT imaged through CTP and NCCT were included. Data were pooled using a random-effects model. The primary outcome of interest was rate of functional independence, defined as modified Rankin scale 0-2. The secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction 2b-3, mortality, and symptomatic intracranial hemorrhage (sICH). Five studies with 3,384 patients were included in our analysis. There were comparable rates of functional independence (odds ratio [OR] 1.03, 95% CI 0.87-1.22; p = 0.71) and sICH (OR 1.09, 95% CI 0.58-2.04; p = 0.80) between the 2 groups. Patients imaged with CTP had higher rates of successful reperfusion (OR 1.31, 95% CI 1.05-1.64; p = 0.015) and lower rates of mortality (OR 0.79, 95% CI 0.65-0.96; p = 0.017). Although recovery of functional independence after late-window EVT was not more common in patients selected by CTP when compared with patients selected by NCCT only, patients selected by CTP had lower mortality.

Endovascular treatment versus no endovascular treatment after 6–24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial

Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]). In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow. Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Outcomes with Endovascular Treatment of Patients with M2 Segment MCA Occlusion in the Late Time Window.

Randomized trials in the late window have demonstrated the efficacy and safety of endovascular thrombectomy in large-vessel occlusions. Patients with M2-segment MCA occlusions were excluded from these trials. We compared outcomes with endovascular thrombectomy in patients with M2-versus-M1 occlusions presenting 6-24 hours after symptom onset. Analyses were on pooled data from studies enrolling patients with stroke treated with endovascular thrombectomy 6-24 hours after symptom onset. We compared 90-day functional independence (mRS ≤ 2), mortality, symptomatic intracranial hemorrhage, and successful reperfusion (expanded TICI = 2b-3) between patients with M2 and M1 occlusions. The benefit of successful reperfusion was then assessed among patients with M2 occlusion. Of 461 patients, 367 (79.6%) had M1 occlusions and 94 (20.4%) had M2 occlusions. Patients with M2 occlusions were older and had lower median baseline NIHSS scores. Patients with M2 occlusion were more likely to achieve 90-day functional independence than those with M1 occlusion (adjusted OR = 2.13; 95% CI, 1.25-3.65). There were no significant differences in the proportion of successful reperfusion (82.9% versus 81.1%) or mortality (11.2% versus 17.2%). Symptomatic intracranial hemorrhage risk was lower in patients with M2-versus-M1 occlusions (4.3% versus 12.2%, P = .03). Successful reperfusion was independently associated with functional independence among patients with M2 occlusions (adjusted OR = 2.84; 95% CI, 1.11-7.29). In the late time window, patients with M2 occlusions treated with endovascular thrombectomy achieved better clinical outcomes, similar reperfusion, and lower symptomatic intracranial hemorrhage rates compared with patients with M1 occlusion. These results support the safety and benefit of endovascular thrombectomy in patients with M2 occlusions in the late window.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

March 2023 Stroke Highlights.

March 2023 Stroke Highlights.

Abstract Number: LBA2 Early versus Late Window in the Endovascular Management of Acute Tandem Lesions

Introduction Despite the irrefutable benefit of mechanical thrombectomy for patients with isolated intracranial large vessel occlusions (LVO), the effect of endovascular treatment in patients with tandem lesions remains unclear. In this study from the multi‐center PICASSO registry, we compare efficacy and safety outcomes in TLs patients treated in the early versus late window. Methods In this study, we used the data from the multi‐center PICASSO (Proximal Internal Carotid Artery Acute Stroke Secondary to Tandem Occlusion Thrombectomy) registry. PICASSO collaboration is a retrospective observational registry from 17 stroke centers. We compared efficacy and safety outcomes in TLs patients treated in the early versus late window. Patients were divided into two groups depending on last known well (LKW) to puncture time: Early time‐window group (&lt;6 hours), and late time‐window group (6‐24 hours).We performed multivariable logistic and multinomial regressions to evaluate the association between each group and efficacy and safety outcomes, Results 628 patients were included in the study. There were 336 (53.5%) treated in the early time‐window and 292 (46.5%) in the late time‐window. We did not observe a statistically significant difference between groups mRS 0–2 at 90 days (46.5% vs. 49%, aOR = 1.51, 95%CI: 0.92‐2.57, p = 0.101), shift analysis of mRS (aOR = 0.93, 95%CI: 0.63‐1.38, p = 0.734), and increased time from LKW to puncture was not significantly associated with mRS 0–2 at 90 days (aOR = 1.05, 95% CI: 0.99‐1.11, p = 0.09 for each hour delay). Similarly, we did not find differences in hemorrhagic transformation of ischemic stroke types: symptomatic ICH (5.1% vs. 4.1%, aOR = 0.80, 95%CI: 0.34‐1.88, p = 0.604), parenchymal hematoma type 2 (8.1% vs. 6.9%. aOR = 0.85, 95%CI: 0.44‐1.66, p = 0.641), and in ordinal analysis of petechial hemorrhage (19.8% vs 24.7%, aOR = 1.15, 95%CI: 0.79‐1.66), p = 0.466). Additionally, there were no differences in rates of successful reperfusion (mTICI 2b‐3) (88.7% vs. 85.2%, aOR = 1.19, 95%CI: 0.67‐2.11, p = 0.546), first pass effect (61.1% vs. 56.9%, aOR = 1.01, 95%CI: 0.65‐1.56, p = 0.963), early neurological improvement (44.1% vs. 36.7%, aOR = 0.96, 95%CI: 0.64‐1.44, p = 0.833), mortality at 90‐days (15.2% vs. 19.2%, aOR = 1.62, 95%CI: 0.94‐2.8, p = 0.81) and in‐hospital mortality (9.8% vs. 10.5%, aOR = 1.28, 95% CI 0.68‐2.39, p = 0.441). Conclusions The therapeutic effect of endovascular therapy in patients with AIS due to tandem lesions who present in the late time‐window is similar to those presenting in the early time‐window. Furthermore, efficacy and safety outcomes rates are consistent with those found in clinical trials that included patients with isolated intracranial lesions treated in the late time‐window.

Abstract Number ‐ 107: Better Late Than Never? ‐ Stroke Revascularization Beyond Day 10: Case Series And Literature Review

Introduction In the last several years,there has been a paradigm shift in treating patients presenting with large vessel occlusion (LVO) strokes with endovascular therapy (EVT). Currently, the 24‐hour window has been incorporated in acute stroke management guidelines based on trials supporting the selection of patients with evidence of ischemic penumbra on perfusion imaging1,2. No current randomized control trials exist to support very late window EVT (beyond 24 hours) from last seen well (LSW) and its benefits are unknown. Several retrospective studies showed that EVT is safe and feasible up to 6 days from LSW in selected patients who are able preserve a favorable ischemic core to penumbra3, 4, 5. In this study we present a retrospective review of three patients with LVO strokes of the anterior circulation successfully treated between 10–14 days from LSW. We aim to explore the safety, efficiency and positive predictors of very late window EVT. Methods A single center retrospective review of stroke patients was performed. 517 patients with LVO strokes who underwent EVT between January 2018 and December 2021 were screened. 3 patients were found to have EVT performed 24 hours beyond LSW. Patient demographics, characteristics and clinical information were collected by systematic chart review. The primary outcome was functional independence as assessed by the modified Rankin Score (mRS) at 90 days. The safety outcomes included neurological deterioration and symptomatic intracranial hemorrhage, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of 4 or more). Further, a comprehensive literature review of studies describing very late window EVT cases indexed in PubMed was performed. Results We identifiedthree patients with LVO strokes, treated more than 24 hours from LSW. Patient ages ranged from 75 to 89 years. Baseline NIHSS ranged from 1 to 13. All patients had LVO or stenosis of the anterior circulation (internal carotid artery and/or M1 segment of the middle cerebral artery). All patients had fluctuation in their symptoms with worsening going from a supine position to a sitting position, evidence of ischemic penumbra on perfusion imaging and slow infarct growth on repeat brain imaging. The time from LSW to intervention ranged from 11 to 14 days. Recanalization score ranged from 2B‐3. No patients had intracranial hemorrhage or neurological decline. mRS scores were 2, 4, and 6 at 3 months. The patient who died had preservation of neurological function but died in the hospital due to heart failure. Conclusions We conclude that widening of the EVT time window presents new opportunities to treat a select population of LVO stroke patients. To our knowledge, there are no other reports of EVT in LVO patients beyond 10 days of LSW. Patients who have evidence of large ischemic penumbra, fluctuation of symptoms with change in position or blood pressure, good collateral circulation, and small infarct core that grows slowly on repeat imaging may be reasonable candidates for delayed EVT. More data are needed to inform clinical practice.

Effect of Petroleum Generation and Retention on Nanopore Structure Change in Laminated and Massive Shales-Insights from Hydrous Pyrolysis of Lacustrine Source Rocks from the Permian Lucaogou Formation.

The lacustrine shale of the Middle Permian Lucaogou Formation in the Jimusar Sag is the principal prospective unconventional target in the Junggar Basin. The effect of petroleum generation and retention on nanopore structure change during thermal maturity in lacustrine shale is still unclear. In this study, two laminated and two massive shale samples from the Permian Lucaogou Formation were selected to study this change by closed hydrous pyrolysis. The pyrolysis temperatures were 295, 320, 345, 370, and 400 °C, which cover from the mature to the post-mature stage. Total organic carbon (TOC), Rock-Eval, and low-pressure N2 adsorption tests on pyrolyzed shale samples before and after extractable organic matter (EOM) extraction were conducted systematically. The results indicate that (1) the petroleum generation on nanopore structure change is in stages. The peak nanopore volume expanding stage is the late oil window (R o = 0.9-1.35%). At the post-mature stage (R o > 1.35%), the mesopore volume decreased and the majority of the nanopore space is from macropores. (2) The presence of EOM decreased both mesopores and macropores in the peak oil window. (3) The organic-rich laminated shale generated more macropores than massive shale with increasing thermal maturity. The results of this study shed light on the dynamic effect of laminae fabric, petroleum generation, and retention on shale nanopore structure change across the oil window.

Abstract WP115: DWI/FLAIR Mismatch Is Common In Late Window Patients With Target Perfusion Mismatch

Introduction: The presence of a DWI/FLAIR mismatch has been suggested as a method to identify patients within 4.5 hours from stroke symptom onset. We studied patients from DEFUSE 2 and 3 with the target perfusion mismatch profile to evaluate the rates of DWI/FLAIR mismatch in patients with who have favorable collaterals in early and late time windows. We hypothesize that the persistence of DWI/FLAIR mismatch in late window patients may reflect good collateral circulation. Methods: We identified 58 eligible patients in D2 and 30 patients from D3. Imaging was reviewed by two neuroradiologists and one neurologist who rated the presence of DWI-FLAIR mismatch. Results: The inter-rater agreement for the presence of DWI/FLAIR mismatch was 88.3%. There were 32 patients who were &lt; 6 hours from last known well (LKW) or symptom onset, 17 patients who were ≥ 6 hours from symptom onset, and 26 patients who were ≥ 6 hours from LKW with an unknown time of symptom onset. These are categorized as early, late, and suspected late window, respectively. The rate of DWI/FLAIR mismatch was 56% in the early window group, 41% in the late window group, and 35% in the suspected late window group. The overall rate of DWI/FLAIR mismatch did not differ significantly between these three groups (56% vs. 41% vs. 35%, p=0.239). Of the early window patients, the rate of DWI-FLAIR mismatch was higher in those with the target perfusion mismatch profile (67%) compared to those without (36%). All but one the known onset late window patients had the target perfusion mismatch profile, and the rate of DWI-FLAIR mismatch in this group was 35%. Forthcoming analyses will include predictors of DWI-FLAIR mismatch such as hypoperfusion intensity ratio, time from symptom onset, and NIHSS score. Conclusions: More than one-third of patients presenting &gt;6 hours from symptom onset with a target perfusion mismatch profile have DWI/FLAIR mismatch. This could reflect the presence of good collateral circulation that may delay the appearance of a FLAIR lesion. The rate of DWI/FLAIR mismatch did not differ among early, late, and expected late window patients. This suggests that, among patients with favorable collaterals, DWI/FLAIR mismatch does not reliably identify early window patients.

Abstract WP98: Utilization Of Perfusion Imaging For Acute Ischemic Stroke: Secular Trends And Effects On Outcomes Of Endovascular Treatment

Introduction: Perfusion imaging (PI) could guide decision-making for endovascular treatment (EVT) of acute ischemic stroke (AIS). However, PI was underused even in the US before the pivotal EVT trials proved its usefulness in 2018. This study aimed to describe the secular trends of PI utilization and investigate the effectiveness of PI-based EVT in real-world practice. Methods: Using a prospective multicenter (n=17) stroke registry in South Korea, we identified patients with AIS who presented within 24 hours from onset between 2011 and 2021. The study period was divided into 3 epochs: 2011-2014, 2015-2017, and 2018-2021. The study population was divided into the early (arrival within 6 hours) and late window (6-24 hours) groups. Results: A total of 51,650 patients (15,654 patients in 2011-2014, 14,432 patients in 2015-2017, and 21,564 patients in 2018-2021) were analyzed. Utilization of PI decreased in the overall population and early window group ( P trend &lt;0.001); 43.3% and 54.1% in 2011-2014, 40.1% and 44.1% in 2015-2017, and 38.4% and 40.2% in 2018-2021, respectively; but increased in the late window group ( P trend &lt;0.001); 31.3% in 2011-2014, 35.7% in 2015-2017, and 36.5% in 2018-2021. Of 10,872 patients with anterior large-vessel occlusion (aLVO), the EVT rate was not different between patients with and without PI (48.7% vs. 46.6%, P =0.08) in the early window but higher in those with PI than without PI in the late window (29.8% vs. 18.7%, P &lt;0.001). The EVT outcome (3-month mRS 0-2) was not different between patients with and without PI in the early window (44.1% vs. 41.8%, P =0.21) and late window (38.4% vs. 39.2%, P =0.81). Propensity score analysis and instrumental variable analysis with PI rate per center as an instrument will be performed to adjust imbalances between patients with and without PI. Conclusion: Between 2011 and 2021 in South Korea, PI utilization has decreased in patients arriving within 6 hours from onset but has increased in those arriving between 6 and 24 hours. Among patients with aLVO, PI likely increased the EVT rate in the late window but did not in the early window. PI utilization did not seem to affect the EVT outcomes, but in-depth analysis is required.

Characteristics and genesis of light oil in Tabei Area, Tarim Basin, Northwestern China

Light oil is a high-quality crude oil. The formation and chemical composition of light oil is a matter of great concern to petroleum geologists. Yakela Field and Shunbei Field, which are located in Yakela and Shunbei regions, respectively, are the two main light oil fields in the Tabei uplift of the Tarim Basin. In order to identify the causative mechanism of light oils in these two fields, 17 crude oil samples were selected and analyzed by gas chromatography (GC) for saturated hydrocarbons and gas chromatography–mass spectrometry (GCMS) for saturated and aromatic biomarkers. Then, the compounds were measured via the mass spectrometry detector after GC separation. The molecular geochemical characteristics showed that the light oils in the two fields are sourced from similar marine source rocks deposited under weak oxidative and reductive environments. The maturity of crude oil in the Shunbei Field is higher than that in the Yakela Field. Simulation results of hydrocarbon generation history of source rocks in two fields showed that the formation mechanism of the two light oils is different. The light oil in the Yakela Field is directly generated by the source rock in the late oil-generating window. The crude oil in the Shunbei Field is formed by the deep burial and maturation of the crude oil generated in the early stage of the source rock.

Endovascular Therapy for Acute Stroke: New Evidence and Indications.

Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke. In the past few years, endovascular treatment indications have expanded to include patients being treated in the extended window, with large ischemic core infarction, basilar artery occlusion (BAO) thrombectomy, as demonstrated by several randomized clinical trials. Intravenous thrombolysis (IVT) bridging to mechanical thrombectomy has also been studied via several randomized clinical trials, with the overall results indicating that IVT should not be skipped in patients who are candidates for both IVT and EVT. Simplification of neuroimaging protocols in the extended window to permit non-contrast CT, CTA collaterals have also expanded access to mechanical thrombectomy, particularly in regions across the world where access to advanced imaging may not be available. Ongoing study of areas to develop include rescue stenting in patients with failed thrombectomy, medium vessel occlusion thrombectomy, and carotid tandem occlusions. In this narrative review, we summarize recent trials and key data in the treatment of patients with large ischemic core infarct, simplification of neuroimaging protocols for the treatment of patients presenting in the late window, bridging thrombolysis, and BAO EVT evidence. We also summarize areas of ongoing study including medium and distal vessel occlusion.

Late Window Imaging Selection for Endovascular Therapy of Large Vessel Occlusion Stroke: An International Survey

Background Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion. Methods We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios. Results There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P &lt;0.0001), and high‐ versus low‐middle income countries (70.5% versus 44.5%; P &lt;0.0001). When presented with a late window patient, 41.6% would complete CT perfusion or magnetic resonance imaging prior to EVT, 25.4% would perform CT perfusion or magnetic resonance imaging prior to IVT and EVT, and 25.8% would refer to EVT without advanced imaging. If advanced imaging was not readily available, 70.1% would refer a patient to EVT based on CT in the late window. Additional time delay within 20 minutes to obtain advanced imaging was considered acceptable in 77.7% of respondents. Conclusion Current guidelines for imaging late window EVT candidates are inconsistent with imaging decisions by physicians. Most respondents consider an imaging delay of greater than 20 minutes unacceptable. Access to advanced imaging was greater in comprehensive stroke centers and high‐income countries. In the case of limited access most respondents would consider EVT based on CT only.

Synthesis of protein vesicles for extending time window of ischemic stroke treatment through microcirculatory thrombolysis

Microcirculatory disturbances are a major barrier to extend the time window of ischemic stroke treatment. Herein, we developed a dynamic template method for the synthesis of protein vesicles, by which urokinase-type plasminogen activator (uPA) was crosslinked by poly(ethylene glycol) via pH sensitive host–guest interaction to form a protein gel-shell to encapsulate superoxide dismutase (SOD) for getting cascade biofunctions of microvessel thrombolysis and reperfusion injury inhibition. On a middle cerebral artery occlusion mouse model, the uPA@SOD vesicles administrated beyond intravenous thrombolysis time window (>4.5 h) could reopen the collateral circulation of brain, thus benefiting the followed interventional recanalization of large vessel in the late window (>6 h). These led to rapid reversion of hypoxia condition and more efficient rescue of injured neurons in the ischemic tissue. The synthesis of protein vesicles is highly beneficial for stroke treatment, meanwhile enabling the facile creation of multi-protein therapeutic systems.

EEG analysis of the visual motion activated vection network in left- and right-handers

Visually-induced self-motion perception (vection) relies on interaction of the visual and vestibular systems. Neuroimaging studies have identified a lateralization of the thalamo-cortical multisensory vestibular network, with left-handers exhibiting a dominance of the left hemisphere and right-handers exhibiting a dominance of the right hemisphere. Using electroencephalography (EEG), we compare the early processing of a vection-consistent visual motion stimulus against a vection-inconsistent stimulus, to investigate the temporal activation of the vection network by visual motion stimulation and the lateralization of these processes in left- versus right-handers. In both groups, vection-consistent stimulation evoked attenuated central event-related potentials (ERPs) in an early (160–220 ms) and a late (260–300 ms) time window. Differences in estimated source activity were found across visual, sensorimotor, and multisensory vestibular cortex in the early window, and were observed primarily in the posterior cingulate, retrosplenial cortex, and precuneus in the late window. Group comparisons revealed a larger ERP condition difference (i.e. vection-consistent stimulation minus vection-inconsistent stimulation) in left-handers, which was accompanied by group differences in the cingulate sulcus visual (CSv) area. Together, these results suggest that handedness may influence ERP responses and activity in area CSv during vection-consistent and vection-inconsistent visual motion stimulation.

Association of Noncontrast Computed Tomography and Perfusion Modalities With Outcomes in Patients Undergoing Late-Window Stroke Thrombectomy

There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy. To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI). In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel occlusion from 2013 to 2021. Patients were selected by NCCT, CTP, and DWI. Admission Alberta Stroke Program Early CT Score (ASPECTS) as well as confounding variables were adjusted. Follow-up duration was 90 days. Data were analyzed from November 2021 to March 2022. Selection by NCCT, CTP, or DWI. Primary outcome was functional independence (modified Rankin scale 0-2) at 90 days. Among 3356 patients, 733 underwent late-window mechanical thrombectomy. The median (IQR) age was 69 (58-80) years, 392 (53.5%) were female, and 449 (65.1%) were White. A total of 419 were selected with NCCT, 280 with CTP, and 34 with DWI. Mean (IQR) admission ASPECTS were comparable among groups (NCCT, 8 [7-9]; CTP, 8 [7-9]; DWI 8, [7-9]; P = .37). There was no difference in the 90-day rate of functional independence (aOR, 1.00; 95% CI, 0.59-1.71; P = .99) after adjusting for confounders. Symptomatic intracerebral hemorrhage (NCCT, 34 [8.6%]; CTP, 37 [13.5%]; DWI, 3 [9.1%]; P = .12) and mortality (NCCT, 78 [27.4%]; CTP, 38 [21.1%]; DWI, 7 [29.2%]; P = .29) were similar among groups. In this cohort study, comparable outcomes were observed in patients in the late window irrespective of neuroimaging selection criteria. Admission NCCT scan may triage emergent large vessel occlusion in the late window.

Duloxetine Exposure During Pregnancyand the Risk of Offspring Being Born Small for Gestational Age or Prematurely: A Nationwide Danish and Swedish Safety Study.

Depression or depressive symptoms are common among pregnant women. The use of antidepressants during pregnancy has grown steadily. The risk of offspring being born small for gestational age or prematurely when exposed to duloxetine during pregnancy is not established. We aimed to investigate the association between duloxetine exposure during pregnancy and offspring being born small for gestational age or prematurely. We conducted an observational study including live births in Sweden and Denmark (2004-2016). Duloxetine exposure during early (0-140 days) or late (141 to delivery) pregnancy compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, venlafaxine-exposed, and duloxetine discontinuers. In total, 2,083,467 pregnancies were identified, where 1589 and 450 were duloxetine exposed in early and late pregnancy, respectively. For small for gestational age, no increased risk was seen for duloxetine across comparators. In the early and late exposure windows, propensity score-matched odds ratios for small for gestational age ranged between 0.64 (95% confidence interval 0.44-0.95) and 1.48 (95% confidence interval 0.85-2.57). For preterm birth, the findings differed across comparators and exposure-time windows, but trended towards an increased risk for duloxetine-exposed when compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, and duloxetine discontinuers in both early exposure and late exposure. The odds ratios ranged between 1.17 and 2.04, of which some did not reach statistical significance. No clear association was observed when compared with venlafaxine exposed, 0.91 (95% confidence interval 0.73-1.14) for early exposure and 1.26 (95% confidence interval 0.86-1.86) for late exposure. Most preterm births (79.2%) occurred in weeks 33-36 of gestation. Duloxetine exposure during pregnancy is unlikely to increase the risk of small for gestational age. Although not consequently statistically significant across comparisons, a trend towards an increased risk of preterm birth was observed for duloxetine exposed. Therefore, an increased risk of preterm birth cannot be excluded, especially for women exposed to duloxetine throughout pregnancy.

Multiparametric Neuroimaging and Its Association with Non-Contrast Computed Tomography in Late-Window Large Vessel Occlusion Acute Stroke

Introduction: Endovascular treatment (EVT) for acute ischemic stroke (AIS) between 6 and 24 h is established as a standard of care among patients selected by multiparametric neuroimaging. We aimed to explore neuroimaging parameters in late-window large vessel occlusion (LVO) patients and its association with non-contrast computed tomography (NCCT) findings. Methods: We included consecutive AIS patients within 6–24 h from the symptoms onset with LVO. We described multiparametric imaging findings, the rate of patients who fulfilled imaging perfusion criteria according to the DAWN and DEFUSE-3 trials that define the computed tomography perfusion mismatch (CTP-MM) group and its association with NCCT focused on Alberta Stroke Program Early CT Score (ASPECTS). We also analyzed the association between neuroimaging parameters and the clinical outcome determined by the 90-day modified Rankin scale (mRS). Results: We included 206 patients, of them, 176 (85.4%) presented CTP-MM and 184 (89.3%) presented an ASPECTS ≥6 on admission. The rate of CTP-MM was 90.8% in patients with ASPECTS ≥6, compared with 40.9% in those with low ASPECTS. ASPECTS was moderately correlated with ischemic core determined by cerebral blood flow <30% volume (rS = −0.557, p < 0.001). In EVT-treated patients (185, 89.8%), after adjusting for identifiable confounders, the presence of CTP-MM was a predictor of 90-day functional independence (OR: 3.38; 95% CI: 1.01–11.29; p = 0.048). We did not find an association between CTP-MM and 90-day functional disability (ordinal mRS shift, aOR: 1.39; 95% CI: 0.58–3.34; p = 0.459). Conclusions: A great majority of patients who presented a LVO in the late window fulfilled guidelines imaging criteria to undergo EVT, especially those with high ASPECTS (≥6). Our data suggest that NCCT with CT angiography could be a reasonable approach for AIS treatment selection also in the late window.

Accuracy of CT perfusion-predicted core in the late window.

Recent endovascular trials have spurred a paradigm shift toward routine use of CT perfusion (CTP) for decision-making in acute ischemic stroke. CTP use in the late window, however, remains under evaluation. Our objective was to assess the accuracy of CTP-predicted core in the late window. In a retrospective review of our prospectively identified stroke registry at a single, comprehensive stroke center, we included patients with anterior large vessel occlusions presenting within the 6-24 h window who underwent baseline CTP evaluation and achieved TICI2b or TICI3 reperfusion on endovascular treatment. We recorded baseline CTP-predicted core volumes at relative cerebral blood flow (CBF) thresholds of <30% <34%, and <38% using RAPID software. Final infarct volumes (FIV) were calculated using follow up MRI and CT, obtained within 72 h after stroke onset. Of the eligible patients, 134 met our inclusion criteria. Mean FIV was 39.5 (SD 49.6). Median CTP to reperfusion time was 93.5 min. Median absolute differences between CTP-predicted core and FIV were 14.7, 14.9, and 16.0 ml at <30%, <34%, and <38%, respectively. Correlation between CTP-predicted ischemic cores and FIV was moderate and statistically significant at all thresholds: r = 0.43 (p <0.001), r = 0.43 (p <0.001), and r = 0.42 (p <0.001) at the <30%, <34%, and <38% cutoffs, respectively. CTP cores in the 6-24 h period underestimate FIV, especially with larger infarcts. CTP-predicted core volumes in the late window show moderate positive correlation with FIV.