Salvageable Brain Research Articles

Acute ischemic stroke treatment

Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are the cornerstones of acute ischemic stroke treatment. While IVT has been an integral part of acute therapy since the mid-1990s, EVT has evolved as one of the most effective treatments in medicine over the past decade. Traditionally, systemic thrombolysis has been performed with alteplase (rtPA). More recently, tenecteplase (TNK) has been shown to be non-inferior to rtPA. TNK has some pharmacological advantages over rtPA and may lead to earlier recanalization, particularly in large vessel occlusions. All recanalization therapies are highly time dependent. To ensure rapid treatment, standard operating procedures (SOPs) should be established and followed in clinical practice. The optimal time window for IVT is 4.5 h after symptom onset and can be extended up to 9 h using specialized imaging techniques. For EVT, studies suggest atime window up to 24 h after symptom onset. In some cases, EVT has been successfully performed beyond this time window. To select patients for EVT, advanced imaging identifying salvageable brain tissue might be necessary. Even in large ischemic stroke, EVT can still improve outcome. Compared to EVT, IVT requires fewer technical and human resources, so more stroke patients can potentially be treated. In contrast, EVT requires highly trained personnel with sophisticated equipment and can, therefore, only be performed in specialized centers. Both procedures should be combined within the 4.5 h time window for patients without contraindications.

Evolving Evidence Practices in Acute Stroke Care

Acute ischemic stroke care is experiencing a transformative shift, driven by emerging evidence supporting optimized thrombolytic strategies, extended treatment windows, and advanced imaging protocols. Recent clinical trials have demonstrated the non-inferiority—and, in certain aspects, superiority—of tenecteplase over alteplase. With its simplified single bolus administration, enhanced fibrin specificity, and potential for improved recanalization rates, tenecteplase is increasingly recognized as a preferred first-line thrombolytic agent in many treatment algorithms. Additionally, streamlined treatment protocols have contributed to reduced door-in and door-out times for patients requiring transfer to higher-level centers for endovascular stroke interventions. The conventional 4.5-hour thrombolysis window is also being redefined. Advanced imaging techniques, such as CT perfusion and diffusion-weighted MRI, now enable the identification of salvageable brain tissue beyond standard time constraints. These technologies have facilitated the safe and effective administration of thrombolytics in carefully selected patients, extending the treatment window to as much as 9 hours post-symptom onset. Wake-up stroke, historically excluded from thrombolytic treatment due to uncertainty around symptom onset time, is now being successfully addressed through imaging-based protocols. Landmark trials, including WAKE-UP and EXTEND, have demonstrated the efficacy and safety of IV thrombolysis in patients showing imaging evidence of salvageable brain tissue, even without a known onset time. Further advancements include the integration of innovative tools, such as electronic fundoscopy, which has improved the timely detection and management of central retinal artery occlusion, ensuring faster intervention and better outcomes for these high-risk patients. Despite these significant advancements, challenges persist in translating evidence into practice. Barriers such as equitable access to advanced imaging, variability in protocol adoption, and healthcare system preparedness continue to impact stroke care delivery. This presentation will synthesize the latest evidence, share clinical insights, and outline practical strategies derived from the experience of an integrated healthcare system in Northern California, comprising 21 stroke centers. Key focus areas include the adoption of tenecteplase over alteplase, leveraging tele-stroke technology for real-time acute care consultation, extending thrombolysis treatment windows, implementing electronic fundoscopy, and optimizing wake-up stroke management protocols.

CT Perfusion Metrics as Indicators of Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Clinical Analysis.

Intracranial Atherosclerotic Stenosis (ICAS) is a prevalent etiology of acute ischemic stroke (AIS), leading to significant morbidity and mortality. The accurate diagnosis and treatment of ICAS-induced AIS are critical to improving outcomes. This study assesses the application of Computed Tomography Perfusion (CTP) in predicting ICAS in AIS patients and its potential impact on patient management. A retrospective analysis was conducted on 224 AIS patients who underwent endovascular therapy (EVT) at one single Chinese Stroke Center between April 2022 and December 2023. Clinical and radiological data were collected, including patients' demographics, CTP parameters, and 90-day modified Rankin Scale (mRS) scores. Logistic regression and receiver operating characteristic (ROC) curves evaluated the predictive power of CTP parameters for ICAS. CTP analysis revealed significant differences in perfusion parameters between ICASinduced AIS and other etiologies. ICAS patients had a smaller ischemic volume on admission and higher mismatch ratios [Time to Maximum, Tmax＞6s: Other Causes: 132.4 [70.5, 183.3] mL, ICAS: 96.3 [79.8, 107.3] mL, P=0.0064; relative cerebral blood flow, rCBF＜30%: Other Causes: 2.4 [0.0, 10.8] mL, ICAS: 0.6 [0.0, 7.0] mL, p =0.0145; mismatch ratio: 7.4 [2.5, 15.0], ICAS: 11.0 [4.6, 17.8], p =0.0285], indicating more salvageable brain tissue. The 90-day mRS showed better functional outcomes in the ICAS group, with a higher likelihood of minimal to no disability [mRS 90 equals 0-1: ICAS: 53.0% vs. Other Causes: 36.3%, p =0.0122]. The predictive model for ICAS, combining clinical manifestations and CTP parameters, yielded an area under the curve (AUC) of 0.7779, demonstrating good diagnostic performance. CTP is a valuable diagnostic tool for ICAS-induced AIS, offering the potential for early identification and informing the decision for endovascular treatment. The positive correlation between CTP findings and patient outcomes supports its utility in clinical practice.

Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial

BackgroundThe performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the...

Clinical and radiographic outcomes after mechanical thrombectomy in medium-vessel posterior cerebral artery occlusions: Subgroup analysis from STAR.

Whereas mechanical thrombectomy (MT) has become standard-of-care treatment for patients with salvageable brain tissue after acute stroke caused by large-vessel occlusions, the results of MT in patients with medium-vessel occlusions (MEVOs), particularly in the posterior cerebral artery (PCA), are not well known. Using data from the international Stroke Thrombectomy and Aneurysm Registry (STAR), we assessed presenting characteristics and clinical outcomes for patients who underwent MT for primary occlusions in the P2 PCA segment. As a subanalysis, we compared the PCA MeVO outcomes with STAR's anterior circulation MeVO outcomes, namely middle cerebral artery (MCA) M2 and M3 segments. Of the 9812 patients in STAR, 43 underwent MT for isolated PCA MeVOs. The patients' median age was 69 years (interquartile range 61-79), and 48.8% were female. The median NIH Stroke Scale score was 9 (range 6-17). After recanalization, 67.4% of patients achieved successful recanalization (modified treatment in cerebral infarction score [mTICI] ≥ 2b), with a first-pass success rate of 44.2%, and 39.6% achieved a modified Rankin score of 0-2 at 90 days. Nine patients (20.9%) had died by the 90-day follow-up. In comparison with M2 and M3 MeVOs, there were no differences in presenting characteristics among the three groups. Patients with PCA MeVOs were less likely to undergo intra-arterial thrombolysis (4.7% PCA vs. 10.1% M2 vs. 16.2% M3, p = 0.046) or to achieve successful recanalization (mTICI ≥ 2b, 67.4%, 86.7%, 82.3%, respectively, p < 0.001); however, there were no differences in the rates of successful first-pass recanalization (44.2%, 49.8%, 52.3%, respectively, p = 0.65). We describe the STAR experience performing MT in patients with PCA MeVOs. Our analysis supports that successful first-pass recanalization can be achieved in PCA MEVOs at a rate similar to that in MCA MeVOs, although further study and possible innovation may be necessary to improve successful PCA MeVO recanalization rates.

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer

Background and purposeIn the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC).MethodsThis real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI.Results120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group.ConclusionThe results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

Role of Endovascular Thrombectomy in Improving the Functional Outcome in Acute Stroke Patients Presenting 6-12 Hours after Stroke Onset

Abstract Background Based on the World Health Organization (WHO) statistics, there are 15 million strokes annually. The aim of the treatment in acute ischemic stroke is rapid restoration of perfusion to the ischemic area by minimizing the time between the occurrence of symptoms and the treatment. This is crucial for saving the salvageable brain tissue (penumbra) by restoration of flow and metabolism to normal Aim of Work The aim of work is to evaluate the safety and efficacy of endovascular thrombectomy (EVT) in patients presenting 6-12 hours from onset of stroke symptoms secondary to large vessel occlusion. Patients and Methods 50 Patients presenting with acute ischemic stroke with causative occlusion of major vessels in anterior circulation, underwent mechanical thrombectomy Results Two-thirds of the patients had their intracranial arterial occlusion at M1 segment of the middle cerebral artery. The median baseline NIHSS score, ASPECTS, and mRS score of the studied patients was 16 (IQR 11-20), 8 (IQR 7-9) and 0 (IQR 0-1), respectively. The median final infarct volume, NIHSS score, ASPECTS post-intervention and mRS score at 90 days of the studied patients was 40 ml (IQR 26.5-70) (P &amp;lt; 0.001), 9 (IQR 4-16) (P &amp;lt; 0.001), 8(IQR 5-9) (P &amp;lt; 0.01), and 2 (IQR1-4) (P &amp;lt; 0.001), respectively and (90 %) of them had revascularization type TICI 2b- 3. More than half of the studied patients (52%) had mRS score at 90 days of ≤ 2 and mortality rate was 12%. Conclusions The current study showed that endovascular thrombectomy techniques are safe and effective in the treatment of acute ischemic stroke.

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy

BackgroundTenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited.MethodsIn a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death.ResultsA total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P=0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively.ConclusionsIn this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.)

Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial

Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. Australian National Health Medical Research Council; Boehringer Ingelheim.

Current State of Evidence for Neuroimaging Paradigms in Management of Acute Ischemic Stroke.

Stroke is the chief differential diagnosis in patient presenting to the emergency room with abrupt onset focal neurological deficits. Neuroimaging, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI), vascular and perfusion imaging, is a cornerstone in the diagnosis and treatment decision-making. This review examines the current state of evidence behind the different imaging paradigms for acute ischemic stroke diagnosis and treatment, including current recommendations from the guidelines. Non-contrast CT brain, or in some centers MRI, can help differentiate ischemic stroke and intracerebral hemorrhage (ICH), a pivotal juncture in stroke diagnosis and treatment algorithm, especially for early window thrombolytics. Advanced imaging such as MRI or perfusion imaging can also assist making a diagnosis of ischemic stroke versus mimics such as migraine, Todd's paresis, or functional disorders. Identification of medium-large vessel occlusions with CT or MR angiography triggers consideration of endovascular thrombectomy (EVT), with additional perfusion imaging help identify salvageable brain tissue in patients who are likely to benefit from reperfusion therapies, particularly in the ≥6 h window. We also review recent advances in neuroimaging and ongoing trials in key therapeutic areas and their imaging selection criteria to inform the readers on potential future transitions into use of neuroimaging for stroke diagnosis and treatment decision making. ANN NEUROL 2024;95:1017-1034.

The impact of large core and late treatment trials: An update on the modelled annual thrombectomy eligibility of UK stroke patients.

To support decisions about thrombectomy provision, we have previously estimated the annual UK population eligible for treatment as ∼10% of stroke admissions. Since then, eight further randomised trials that could alter the eligibility rate have reported in 2021-23. We updated our estimates of the eligible population from these trials and other recent studies. An updated decision tree describing the EVT eligible population for UK stroke admissions was produced. Decision criteria were derived from the highest level of evidence available. For nodes where no specific RCT data existed, evidence was obtained from the latest systematic review(s) or the highest quality observational data. We estimate that 15,420 (approximately 15%) of admitted UK stroke patients are now eligible for thrombectomy, or 14,930 if advanced brain imaging using MRI/CT perfusion or collateral assessment were used in all patients. This is a 54% increase in our previous estimate in 2021. Over 50% of LAO strokes are now potentially eligible for thrombectomy. The increase in eligibility is principally due to a much larger cohort of later presenting and/or larger ischaemic core patients. Most previously independent LAO stroke patients presenting within 24 h, even in the presence of a large ischaemic core on initial non-contrast CT, should be considered for thrombectomy with use of advanced brain imaging in those presenting beyond 12 h to identify salvageable penumbral brain tissue. Treatment in most patients remains critically time-dependent and our estimates should be interpreted with this in mind.

Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo.

Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged. Moreover, we revealed ischaemic pericytes to be fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 h post stroke. Despite sustaining acute membrane damage, we observed that over half of all cortical pericytes survived ischaemia and responded to vasoactive stimuli, upregulated unique transcriptomic profiles and replicated. Finally, we demonstrated the delayed recovery of capillary diameter by ischaemic pericytes after reperfusion predicted vessel reconstriction in the subacute phase of stroke. Cumulatively, these findings demonstrate that surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischaemic stroke.

Abstract 242: Clinical Validation Trial Of BraiN20® Medical Device. PROMISE20 Study Protocol

Introduction N20 somatosensory evoked potential (SEP) response shows high predictive accuracy of functional recovery in patients with Acute Ischemic Stroke (AIS) undergoing endovascular thrombectomy (https://www.clinicaltrials.gov/ct2/show/NCT04099615; SVIN Journal, in press). This capacity is independent and even higher than clinical and advanced imaging variables. This study aims to validate BraiN20®, a portable, non‐invasive, AI‐based device to monitor in real‐time the presence and characteristics of N20 in AIS. Methods 65 patients with AIS and anterior Large Vessel Occlusion (LVO) undergoing EVT within 24 hours from onset are included in three comprehensive stroke centers of Catalonia, Spain. Eligibility criteria are no significant pre‐stroke functional dependence, baseline NIHSS score equal or higher than 6 points, occlusion (mTICI 0‐1) of the intracranial ICA, MCA‐M1 or M2 suitable for EVT per local protocols, without infarct volume restrictions measured by ASPECT score or by CTP/DWI‐MRI prior to EVT . The primary objective is to confirm an optimal/good reliability of N20 registration before EVT higher than 75% by two blind expert neurophysiologists, assuming a true proportion equal to 87.5%. Secondary endpoints are the predictive accuracy of N20 response recorded by BraiN20® before and after EVT on functional outcome evaluated by the mRS at 7 and 90 days and analyzed by using Receiving Operating Characteristic curves. A futility interim analysis is planned after the inclusion of 25% of the sample. Results The trial is sponsored by Time is Brain S.L. and will start early September 2023. Primary endpoint results are expected by the end of this year. Conclusion BraiN20® could be a useful medical device to predict salvageable brain and functional recovery of patients along the stroke chain.

Current and Emerging Endovascular and Neurocritical Care Management Strategies in Large-Core Ischemic Stroke.

The volume of infarcted tissue in patients with ischemic stroke is consistently associated with increased morbidity and mortality. Initial studies of endovascular thrombectomy for large-vessel occlusion excluded patients with established large-core infarcts, even when large volumes of salvageable brain tissue were present, due to the high risk of hemorrhagic transformation and reperfusion injury. However, recent retrospective and prospective studies have shown improved outcomes with endovascular thrombectomy, and several clinical trials were recently published to evaluate the efficacy of endovascular management of patients presenting with large-core infarcts. With or without thrombectomy, patients with large-core infarcts remain at high risk of in-hospital complications such as hemorrhagic transformation, malignant cerebral edema, seizures, and others. Expert neurocritical care management is necessary to optimize blood pressure control, mitigate secondary brain injury, manage cerebral edema and elevated intracranial pressure, and implement various neuroprotective measures. Herein, we present an overview of the current and emerging evidence pertaining to endovascular treatment for large-core infarcts, recent advances in neurocritical care strategies, and their impact on optimizing patient outcomes.

The collateral map: prediction of lesion growth and penumbra after acute anterior circulation ischemic stroke

ObjectivesThis study evaluated the collateral map’s ability to predict lesion growth and penumbra after acute anterior circulation ischemic strokes.MethodsThis was a retrospective analysis of selected data from a prospectively collected database. The lesion growth ratio was the ratio of the follow-up lesion volume to the baseline lesion volume on diffusion-weighted imaging (DWI). The time-to-maximum (Tmax)/DWI ratio was the ratio of the baseline Tmax > 6 s volume to the baseline lesion volume. The collateral ratio was the ratio of the hypoperfused lesion volume of the phase_FU (phase with the hypoperfused lesions most approximate to the follow-up DWI lesion) to the hypoperfused lesion volume of the phase_baseline of the collateral map. Multiple logistic regression analyses were conducted to identify independent predictors of lesion growth. The concordance correlation coefficients of Tmax/DWI ratio and collateral ratio for lesion growth ratio were analyzed.ResultsFifty-two patients, including twenty-six males (mean age, 74 years), were included. Intermediate (OR, 1234.5; p < 0.001) and poor collateral perfusion grades (OR, 664.7; p = 0.006) were independently associated with lesion growth. Phase_FUs were immediately preceded phases of the phase_baselines in intermediate or poor collateral perfusion grades. The concordance correlation coefficients of the Tmax/DWI ratio and collateral ratio for the lesion growth ratio were 0.28 (95% CI, 0.17–0.38) and 0.88 (95% CI, 0.82–0.92), respectively.ConclusionPrecise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. Further studies are needed to generalize the findings of this study.Clinical relevance statementPrecise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments.Key Points• Cell viability in cerebral ischemia due to proximal arterial steno-occlusion mainly depends on the collateral circulation.• The collateral map shows salvageable brain extent, which can survive by recanalization treatments after acute anterior circulation ischemic stroke.• Precise estimation of salvageable brain makes it possible to make patient-specific treatment decision.

Predicting severe disability or death in endovascular thrombectomy with large computed tomography perfusion core infarction and limited penumbra.

Patients presenting with large core infarctions benefit from treatment with endovascular thrombectomy (EVT), with a notable 50% reduction in rates of severe disability (modified Rankin Scale [mRS] 5) at 90 days. We studied the ability of previously reported prognostic scales to predict devastating outcomes in patients with a large ischemic core and limited salvageable brain tissue. Retrospective analysis from a health system's code stroke registry, including consecutive thrombectomy patients from November 2017 to December 2022 with an anterior circulation large vessel occlusion, computed tomography perfusion core infarct ≥ 50 ml, and mismatch volume < 15 ml or mismatch ratio < 1.8. Previously reported scales were compared using logistic regression and area under the curve (AUC) analyses to predict 90-day mRS 5-6. Sixty patients (mean age 62.38 ± 14.25 years, median core volume 103 ml [74.75-153]) met inclusion criteria, of whom 27 (45%) had 90-day mRS 5-6. The Charlotte Large artery occlusion endovascular therapy Outcome Score (CLEOS) (odds ratio [OR] 1.35, 95% CI [1.14-1.60], p = 0.0005), Houston Intra-Arterial Therapy-2 (OR 1.35, 95% CI [1.00-1.83], p = 0.0470), and Totaled Health Risks in Vascular Events (OR 1.53, 95% CI [1.07-2.18], p = 0.0199) predicted the primary outcome in the logistic regression analysis. CLEOS performed best in the AUC analysis (AUC 0.83, 95% CI [0.72-0.94]). CLEOS predicts devastating outcomes after EVT in patients with large core infarctions and small volumes of ischemic penumbra.

Tissue Clock Beyond Time Clock: Endovascular Thrombectomy for Patients With Large Vessel Occlusion Stroke Beyond 24 Hours.

Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0-2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients' age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Intravenous thrombolysis of ischemic stroke-Current status

Intravenous thrombolysis (IVT) treatment with alteplase (rtPA) is an essential part of the routine treatment of patients with ischemic stroke since its introduction in the late 1990s. Rapid treatment is of essential importance. For patients with an unclear time window, various mismatch concepts have been established to identify salvageable brain tissue prior to IVT. Numerous official contraindications for rtPA are not evidence-based; for example, current data from observational studies show that systemic thrombolytic treatment is possible even in patients receiving direct oral anticoagulant (DOAC) treatment. Tenecteplase (TNK) is an alternative thrombolytic agent with some pharmacologic advantages. The most recent guidelines indicate that TNK is particularly advantageous over rtPA in patients treated in combination with endovascular stroke therapy (EST). The combination of IVT and EST should primarily be performed in the 4.5‑h time window in patients without contraindications; in the later time window EST alone is conceivable if it can be performed without delay.

CDC42 Might Be a Molecular Signature of DWI-FLAIR Mismatch in a Nonhuman Primate Stroke Model.

No definitive blood markers of DWI-FLAIR mismatch, a pivotal indicator of salvageable ischemic penumbra brain tissue, are known. We previously reported that CDC42 and RHOA are associated with the ischemic penumbra. Here, we investigated whether plasma CDC42 and RHOA are surrogate markers of DWI-FLAIR mismatch. Sixteen cynomolgus macaques (3 as controls and 13 for the stroke model) were included. Guided by digital subtraction angiography (DSA), a middle cerebral artery occlusion (MCAO) model was established by occluding the middle cerebral artery (MCA) with a balloon. MRI and neurological deficit scoring were performed to evaluate postinfarction changes. Plasma CDC42 and RHOA levels were measured by enzyme-linked immunosorbent assay (ELISA). The stroke model was successfully established in eight monkeys. Based on postinfarction MRI images, experimental animals were divided into a FLAIR (-) group (N = 4) and a FLAIR (+) group (N = 4). Plasma CDC42 in the FLAIR (-) group showed a significant decrease compared with that in the FLAIR (+) group (p < 0.05). No statistically significant difference was observed for plasma RHOA. The FLAIR (-) group showed a milder neurological function deficit and a smaller infarct volume than the FLAIR (+) group (p < 0.05). Therefore, plasma CDC42 might be a new surrogate marker for DWI-FLAIR mismatch.

Abstract 48: Outcomes And Risk Of Hemorrhagic Transformation Following Mechanical Thrombectomy In Primary Distal Posterior Cerebral Artery Occlusions-subgroup Analysis From STAR

Background: While mechanical thrombectomy (MT) has become the standard of care for acute stroke patients presenting with large vessel occlusion (LVO) and salvageable brain tissue, limited data is currently available regarding the benefits of MT in patents with medium vessel occlusions (MeVO) especially in the posterior circulation (P2 occlusions). Methods: We used the Stroke Thrombectomy and Aneurysm registry (STAR) which included data from 35 stroke centers in North America, Europe, Asia, and South America. We included patients who presented with MeVO in the M2, M3 or P2 segments and underwent MT. We used a Generalized Linear Model to assess the relationship between location of occlusion and outcomes. Results: 9812 patients were included in STAR at the time of this analysis; 43 underwent MT for P2 occlusion, 130 underwent MT for M3 occlusion; and 1273 underwent MT for M2 occlusion. There was no difference in age, sex, race, rate of IV-tPA and stroke severity between patients in all 3 groups (Table 1). There was a trend toward lower rate of atrial fibrillation in patients with P2 and M3 occlusions. Patients with P2 occlusions were less likely to achieve successful recanalization (modified treatment in cerebral infarction score≥2b); intraarterial thrombolysis was used less in P2 occlusions (4.7% compared to 16.2% in M3 occlusions and 10.1% in M2 occlusions). However, there was no difference in the rate of successful first pass. On multivariable analysis, P2 occlusions were not associated with hemorrhagic transformation (OR 2.0, 95% CI 0.7-5.7, P 0.186), 90-day mortality (OR 0.5, 95% CI 0.2-1.4, P 0.183), or 90-day favorable outcome (OR 2.0, 95% CI 0.9-4.4, P 0.084). Conclusions: In this multicenter study, there was no significant difference in safety and efficacy of MT in patients with MeVOs in posterior circulation (P2 occlusions) compared to M2 and M3 occlusions. Improved techniques for successful recanalization are needed for posterior circulation MeVOs.