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Objective: Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.Methods: We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).Results: Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).Interpretation: The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis. [ABSTRACT FROM AUTHOR]

Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. [ABSTRACT FROM AUTHOR]

Background: This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD).Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.Results: The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B).Conclusions: Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization. [ABSTRACT FROM AUTHOR]

This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available. [ABSTRACT FROM AUTHOR]

Background: In patients with an acute ischemic stroke, the penumbra is defined as ischemic tissue that remains salvageable when reperfusion occurs. However, the expected clinical recovery congruent with penumbral salvage is not always observed., Aims: We aimed to determine whether the magnetic resonance imaging (MRI)-defined penumbra includes irreversible neuronal loss that impedes expected clinical recovery after reperfusion., Methods: In the prospective French Acute Multimodal Imaging Study to Select Patients for Mechanical Thrombectomy (FRAME) and an observational cohort of patients with large vessel occlusions undergoing endovascular treatment, we quantified penumbral integrity by fluid-attenuated inversion recovery (FLAIR) changes. We studied the influence of recanalization status on the evolution of penumbral FLAIR changes and studied penumbral FLAIR changes as predictor of tissue fate and functional outcome on the 90-day modified Rankin Scale (mRS)., Results: Recanalization status did not modify the evolution of rFLAIR signal intensity (SI) over time in the total cohort, but was associated with lower SI in the FRAME subset (b = -0.06, p for interaction = 0.04). Median rFLAIR SI was higher at baseline in the subsequently infarcted penumbra compared to the salvaged (ratio = 1.07, standard deviation (SD) = 0.07 vs 1.03, SD = 0.06 p < 0.0001, n = 150). The severity and extent of rFLAIR SI changes did not predict 90-day functional outcome in univariate (p = 0.09) and multivariate logistic regression (p = 0.4)., Conclusions: Recanalization status did not influence the evolution of penumbral FLAIR changes. FLAIR SI changes in the baseline penumbra were associated with tissue fate, but not functional outcome., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.S. reports grants from Research Foundation Flanders and the Belgian American Educational Foundation during the conduct of the study; other (congress participation) from Daiichi Sankyo outside the submitted work. R.L. has no personal disclosures, but reports consultancy fees paid to the institution from iSchemaView and Boehringer Ingelheim. J.-M.O. reports consultancy fees from Abbvie, Acticor, and Bioxodes and speaker fees from Boehringer Ingelheim and Bristol Myers Squibb. C.C. reports consultant for MicroVention, Medtronic, Stryker, Cerenovus, and MIVI. J.J.H. is a consultant for Medtronic and MicroVention and is a member of the medical and scientific advisory board for iSchemaView.

Background: Hyperintense acute reperfusion marker (HARM) refers to delayed enhancement in the subarachnoid or subpial space on post-contrast fluid attenuated inversion recovery (FLAIR) images. HARM is a measure of blood-brain barrier breakdown, which has been correlated with poor outcomes in patients with acute ischemic stroke with large vessel occlusion (AIS-LVO). We hypothesized that unfavorable venous outflow (VO) would be correlated with HARM after thrombectomy treatment of AIS-LVO., Objective: To determine whether poor VO is associated with HARM on follow-up MRI after stroke in patients with AIS-LVO., Methods: Patients with AIS-LVO from the prospective CRISP2 and DEFUSE2 studies with a baseline CT angiography (CTA) scan and a follow-up MRI with FLAIR sequence were screened for enrollment. VO was measured on the baseline CTA scan using the cortical venous opacification score (COVES). HARM was determined on FLAIR sequences at the follow-up MRI. The primary outcome was the occurrence of HARM between those with good VO (VO+; COVES 3-6) and bad VO (VO-; COVES 0-2)., Results: 121 patients were included; 60.3% (n=73) had VO+ and 39.7% (n=48) had VO-. Patients with VO- had higher presentation National Institutes of Health Stroke Scale scores (18 (IQR 12-20) vs 12 (IQR 8-16) in VO+; P<0.001). Middle cerebral artery M1 segment occlusions were more common in VO- patients (65% vs 43% VO+; P=0.028). VO- patients also had a larger pre-treatment ischemic core (23 (4-44) mL vs 12 (3-22) mL in VO+; P=0.049) and Tmax >6 s volumes (105 (72-142) mL vs 66 (35-95) mL in VO+; P<0.001). VO- patients were more likely to develop HARM after thrombectomy (31% vs 10% in VO+; P=0.003). On multivariable regression analysis, VO- (OR=3.6 (95% CI 1.2 to 10.6); P=0.02) and the presence of any ICH (OR=3.6 (95% CI 1.2 to 10.5); P=0.02) were independently associated with the occurrence of HARM., Conclusions: In patients with AIS-LVO, VO- correlated with HARM on post-thrombectomy MRI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Acute ischemic stroke patients with a large vessel occlusion (LVO) who present to a primary stroke center (PSC) often require transfer to a comprehensive stroke center (CSC) for thrombectomy. Not much is known about specific characteristics at the PSC that are associated with infarct growth during transfer. Gaining more insight into these features could aid future trials with cytoprotective agents targeted at slowing infarct growth. We aimed to identify baseline clinical and imaging characteristics that are associated with fast infarct growth rate (IGR) during interhospital transfer., Methods: We included patients from the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project, a prospective multicenter study. Patients with an anterior circulation LVO who were transferred from a PSC to a CSC for consideration of thrombectomy were eligible if imaging criteria were fulfilled. A CT perfusion (CTP) needed to be obtained at the PSC followed by an MRI at the CSC, before consideration of thrombectomy. The interhospital IGR was defined as the difference between the infarct volumes on MRI and CTP, divided by the time between the scans. Multivariable logistic regression was used to determine characteristics associated with fast IGR (≥5 mL/h)., Results: A total of 183 patients with a median age of 74 years (interquartile range 61-82), of whom 99 (54%) were male and 82 (45%) were fast progressors, were included. At baseline, fast progressors had a higher NIH Stroke Scale score (median 16 vs 13), lower cerebral blood volume index (median 0.80 vs 0.89), more commonly poor collaterals on CT angiography (35% vs 13%), higher hypoperfusion intensity ratios (HIRs) (median 0.51 vs 0.34), and larger core volumes (median 11.80 mL vs 0.00 mL). In multivariable analysis, higher HIR (adjusted odds ratio [aOR] for every 0.10 increase 1.32 [95% CI 1.10-1.59]) and larger core volume (aOR for every 10 mL increase 1.54 [95% CI 1.20-2.11]) remained independently associated with fast IGR., Discussion: Fast infarct growth during interhospital transfer of acute stroke patients is associated with imaging markers of poor collaterals on baseline imaging. These markers are promising targets for patient selection in cytoprotective trials aimed at reducing interhospital infarct growth.

Objectives: This study aimed to compare clinical and perfusion imaging profiles in acute ischemic stroke with large vessel occlusion (AIS-LVO) between patients with intracranial atherosclerotic disease (ICAD) and non-ICAD who underwent endovascular treatment (EVT)., Methods: Data from AIS-LVO patients over the anterior circulation undergoing EVT across two stroke centers were retrospectively analyzed. Clinical profiles and perfusion parameters from automated processing of perfusion imaging were compared between ICAD and non-ICAD groups. Ischemic core was defined as relative cerebral blood flow < 30 % on CT perfusion or apparent diffusion coefficient ≤ 620 × 10 -6 mm 2 /s on MR diffusion weighted imaging., Results: A total of 111 patients were included (46 ICAD, 65 non-ICAD). The ICAD group exhibited a higher male proportion (60.9 % vs. 35.4 %), more M1 segment occlusions (78.3 % vs. 56.9 %), lower atrial fibrillation rates (17.4 % vs. 63.1 %), and lower baseline NIH Stroke Scale (NIHSS) scores (median [IQR]: 13 [8.75-18] vs. 15 [10-21]) at presentation compared to non-ICAD (all p < 0.05). However, there was no difference in NIHSS scores at discharge or in good functional outcomes (modified Rankin Scale 0-2) at 3 months between the two groups. ICAD patients also had smaller median ischemic core volumes (0 [IQR 0-9.7] vs. 4.4 [0-21.6] ml, p = 0.038), smaller median Tmax >6s tissue volulmes (89.3 [IQR 51.1-147.1] vs. 124.4 [80.5-178.6] ml, p = 0.017) and lower median HIR (hypoperfusion intensity ratio defined as Tmax >10s divided by Tmax >6s; 0.28 [IQR 0.09-0.42] vs. 0.44 [0.24-0.60], p = 0.003). Higher baseline NIHSS scores correlated with larger Tmax >6s lesion volumes as well as higher HIR value in non-ICAD patients, but not in ICAD patients., Conclusions: In anterior circulation of AIS-LVO, ICAD patients exhibited distinct clinical presentations and perfusion imaging characteristics when compared to non-ICAD patients. Perfusion imaging profiles may serve as indicators for identifying ICAD patients before EVT., Competing Interests: Declaration of competing interest Hung-Yu Liu, Jeremy J. Heit, Nicole Yuen, Chung-Han Yang, Michael Mlynash, Aroosa Zamarud, Ronda Lun and Maarten G. Lansberg declare no conflicts of interest. Gregory W. Albers has served as a consultant for Genentech and iSchemaView., (Copyright © 2024. Published by Elsevier Inc.)

Background: Robust venous outflow (VO) profiles, measured by degree of venous opacification on pre-thrombectomy CT angiography (CTA) studies, are strongly correlated with favorable outcomes in patients with large vessel occlusion acute ischemic stroke treated by thrombectomy. However, VO measurements are laborious and require neuroimaging expertise., Objective: To develop a semi-automated method to measure VO using CTA and CT perfusion imaging studies., Methods: We developed a graphical interface using The Visualization Toolkit, allowing for voxel selection at the confluence and bilateral internal cerebral veins on CTA along with arterial input functions (AIFs) from both internal carotid arteries. We extracted concentration-time curves from the CT perfusion study at the corresponding locations associated with AIF and venous output function (VOF). Outcome analyses were primarily conducted by the Mann-Whitney U and Jonckheere-Terpstra tests., Results: Segmentation at the pre-selected AIF and VOF locations was performed on a sample of 97 patients. 65 patients had favorable VO (VO+) and 32 patients had unfavorable VO (VO-). VO+ patients were found to have a significantly shorter VOF time to peak (8.26; 95% CI 7.07 to 10.34) than VO- patients (9.44; 95% CI 8.61 to 10.91), P=0.007. No significant difference was found in VOF curve width and the difference in time between AIF and VOF peaks., Conclusions: Time to peak of VOF at the confluence of sinuses was significantly associated with manually scored venous outflow. Further studies should aim to understand better the association between arterial inflow and venous outflow, and capture quantitative metrics of venous outflow at other locations., Competing Interests: Competing interests: GA, NY, MM, TDF, MGL have no relevant relationships to disclose. SC discloses equity and consulting for iSchemaView. GWA discloses equity and consulting for iSchemaView and consulting for Genentech. JF discloses grants and personal fees from Acandis, Cerenovus, MicroVention,Medtronic, and Stryker; grants from Route 92; and personal fees from Phenox and Penumbra outside of the submitted work. JJH discloses consulting for Medtronic and MicroVention and membership of the medical and scientific advisory board for iSchemaView., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Material-specific reconstructions of dual-energy CTA (DECTA) can highlight iodinated contrast, subtract predefined materials, and reduce metal artifact. We present a technique to improve detection of residual aneurysms after endovascular coiling by which iodine-map DECTA (IM-DECTA) reconstructions subtract platinum coil artifacts in MIP images (MIP IM-DECTA) and assess if IM-DECTA offers improved detection over conventional CTA (CCTA) or monoenergetic DECTA., Materials and Methods: We included consecutive patients who underwent endovascular aneurysm coiling with follow-up DECTA and DSA within 24 months. DECTA was performed at 80- and 150-kVp tube voltages on a rapid kV-switching single-source Revolution scanner. CCTA and IM-DECTA series were reconstructed. Reference-standard DSA was compared with CCTA, 50- and 70-keV virtual monochromatic DECTA, IM-DECTA, and MIP IM-DECTA. Blinded to DSA data, cross-section images were reviewed in consensus by 3 neurointerventionalists for residual aneurysms and assigned modified Raymond-Roy classifications (mRRC). Sensitivity, specificity, and accuracy of each series is reported relative to DSA, and single-factor ANOVA and pair-wise Spearman correlation coefficients compared the accuracy of each series. Readers provided ROI measurements of HU deviation adjacent to the aneurysm neck for quantitative noise assessment and qualitatively scored each series on a 3-point Likert-style scale ranging from uninterpretable to excellent image quality., Results: Twenty-one patients with 25 coiled aneurysms were included. Mean time from DECTA to DSA was 286 ± 212 days. IM-DECTA and MIP IM-DECTA most sensitively (89% and 90%) and specifically (93% and 93%) detected residual aneurysms relative to CCTA (6% and 86%). Relative to DSA, IM-DECTA and MIP IM-DECTA most accurately detected (92% versus 28% for CCTA) and classified residual aneurysms by mRRC (ρ C-CTA = -0.08; ρ IM = 0.50; ρ IM-MIP = 0.55; P  < .001). Reader consensus reported the best image quality at the aneurysm neck with IM-DECTA and MIP IM-DECTA, with 56% of CCTAs considered uninterpretable versus 0% of IM-DECTAs, and image noise was significantly lower for IM-DECTA (27.9 ± 3.6 HU) or MIP IM-DECTA (26.8 ± 3.5 HU) than CCTA (103.2 ± 13.3 HU; P  < .001)., Conclusions: MIP IM-DECTA can subtract coil mass artifact and is more sensitive and specific than CCTA for the detection of residual aneurysms after endovascular coiling., (© 2024 by American Journal of Neuroradiology.)

Background: Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with adverse neurological outcomes. Early and accurate diagnosis of DCI is crucial to prevent cerebral infarction. This study aimed to assess the diagnostic accuracy and interrater agreement of the visual assessment of neuroimaging perfusion maps to detect DCI in patients suspected of vasospasm after aSAH., Methods: In this case-control study, cases were adult aSAH patients with DCI who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging in the 24 h prior to digital subtraction angiography for vasospasm diagnosis. Controls were patients with dizziness and no aSAH on CTP imaging. Three independent raters, blinded to patients' clinical information, other neuroimaging studies, and angiographic results, visually assessed anonymized perfusion color maps to classify patients as either having DCI or not. Tmax delay was classified by symmetry into no delay, unilateral, or bilateral., Results: Perfusion imaging of 54 patients with aSAH and 119 control patients without aSAH was assessed. Sensitivities for DCI diagnosis ranged from 0.65 to 0.78, and specificities ranged from 0.70 to 0.87, with interrater agreement ranging from 0.60 (moderate) to 0.68 (substantial)., Conclusion: Visual assessment of perfusion color maps demonstrated moderate to substantial accuracy in diagnosing DCI in aSAH patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Heit is a consultant for Medtronic, MicroVention, iSchemaView and a member of advisory boards for iSchemaView, Balt, and MicroVention.Dr Albers reports equity and consulting for iSchemaView and consulting from Medtronic and Genetech.Dr Steinberg is consultant for Sanbio, Zeiss and Surgical Theatre, patents with Peter Lazic, US.Dr Sussman is a consultant for Cerenovus and Balt.

Background: The occurrence of delayed cerebral ischemia and vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in high morbidity and mortality, but the diagnosis remains challenging. This study aimed to identify neuroimaging perfusion parameters indicative of delayed cerebral ischemia in patients with suspected vasospasm., Methods: This is a case-control study. Cases were adult aSAH patients who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging ≤ 24 h before digital subtraction angiography performed for vasospasm diagnosis and treatment. Controls were patients without aSAH who underwent CTP. Quantitative perfusion parameters at different thresholds, including Tmax 4-6-8-10 s delay, cerebral blood flow and cerebral blood volume were measured and compared between cases and controls. The Vasospasm Index Score was calculated as the ratio of brain volume with time-to-max (Tmax) delay > 6 s over volume with Tmax > 4 s., Results: 54 patients with aSAH and 119 controls without aSAH were included. Perfusion parameters with the strongest prediction of vasospasm on cerebral angiography were the combination of the Vasospasm Index Score (Tmax6/Tmax4) + CBV ≤ 48 % (area under the curve value of 0.85 [95 % CI 0.78-0.91]) with a sensitivity of 63 % and specificity of 95 %., Conclusion: The Vasospasm Index Score in combination with CBV ≤ 48 % on cerebral perfusion imaging reliably identified vasospasm as the cause of DCI on perfusion imaging., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Heit is a consultant for Medtronic, MicroVention, iSchemaView and a member of advisory boards for iSchemaView, Balt, and MicroVention. Dr Albers reports equity and consulting for iSchemaView and consulting from Medtronic and Genetech. Dr. Steinberg is consultant for Sanbio, Zeiss and Surgical Theatre, patents with Peter Lazic, US. Dr Sussman is a consultant for Cerenovus and Balt.., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Deep venous outflow (VO) may be an important surrogate marker of collateral blood flow in acute ischemic stroke patients with a large vessel occlusion (AIS-LVO). Researchers have yet to determine the relationship between deep VO status in late-window patients and imaging measures of collaterals, which are key in preserving tissue., Materials and Methods: We performed a multicenter retrospective cohort study on a subset of DEFUSE 3 patients recruited across 38 centers between May 2016 and May 2017 who underwent successful thrombectomy revascularization. Internal cerebral vein opacification was scored on a scale of 0-2. This metric was added to the cortical vein opacification score to derive the comprehensive VO (CVO) score from 0 to 8. Patients were stratified by favorable (ICV+) and unfavorable (ICV-) ICV scores, and similarly CVO+ and CVO-. Analyses comparing outcomes were primarily conducted by Mann-Whitney U and χ 2 tests., Results: Forty-five patients from DEFUSE 3 were scored and dichotomized into CVO+, CVO-, ICV+, and ICV- categories, with comparable demographics. Hypoperfusion intensity ratio, a marker of tissue level collaterals, was significantly worse in the ICV- and CVO- groups (p = 0.005). ICV- alone was also associated with a larger perfusion lesion (138 ml vs 87 ml; p = 0.023). No significant differences were noted in functional and safety outcomes., Conclusions: Impaired deep venous drainage alone may be a marker of poor tissue level collaterals and a greater degree of affected tissue in AIS-LVO patients presenting in the late-window who subsequently undergo successful revascularization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.C. discloses equity and consulting for iSchemaView. G.W.A. discloses equity and consulting for iSchemaView and consulting for Genentech. J.F. discloses grants and personal fees from Acandis, Cerenovus, MicroVention,Medtronic, and Stryker, grants from Route 92, and personal fees from Phenox and Penumbra outside of the submitted work. J.J.H. discloses consulting for Medtronic and MicroVention and membership of the medical and scientific advisory board for iSchemaView.

Background: Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome., Methods: We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately., Results: A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59-3.71; p  < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37-0.98; p  = 0.044)., Conclusion: Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer., Data Access Statement: The data that support the findings of this study are available upon reasonable request., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr J.J.H. reports consulting fees from Medtronic and MicroVention, and he is a member of the medical and scientific advisory board for iSchemaView; Dr G.W.A. reports stock holdings in iSchemaView; compensation from Biogen, iSchemaView, and Genentech for consultant services. Other authors have nothing to disclose.

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P  < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging ( β estimate, 5.50, 95% CI, 3.81-7.19, P  < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Laurens WINKELMEIER reports no disclosure.Dr Jeremy J. HEIT reports consulting for Medtronic and MicroVention and Medical and Scientific Advisory Board membership for iSchemaView.Dr Gabriel BROOCKS reported receiving personal fees from Eppdata GmbH and compensation as a speaker from Balt outside the submitted work.Julia PRÜTER reports no disclosure.Dr Christian HEITKAMP reports no disclosure.Maximilian SCHELL reports no disclosure.Dr Gregory W. ALBERS reports equity and consulting for iSchemaView and consulting from Medtronic.Dr Maarten G. LANSBERG reports no disclosure.Dr Max WINTERMARK reports grants and funding from the NIH under the grant numbers (1U01 NS086872-01, 1U01 NS087748-01 and 1R01 NS104094).Dr André KEMMLING reports a research collaboration agreement with Siemens Healthcare (company involved in CT/MRI distribution).Dr Christian Paul STRACKE reports no disclosure.Dr Adrien GUENEGO reports no disclosure.Dr Daniel PAECH reports no disclosure.Dr Jens FIEHLER reports grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, Phenox and grants from Route 92 outside the submitted work.Dr Tobias D. FAIZY reports grants from the German Research Foundation (DFG) during the conduct of the study.

Importance: Stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this bias remains unclear., Objective: To investigate the association between poststroke disability and the rate of recurrent stroke during long-term follow up., Design, Setting, and Participants: This cohort study is a post hoc analysis of the Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) and Insulin Resistance Intervention After Stroke (IRIS) secondary prevention clinical trial datasets. PRoFESS enrolled patients from 2003 to 2008, and IRIS enrolled patients from 2005 to 2015. Data were analyzed from September 23, 2023, to May 16, 2024., Exposure: The exposure was poststroke functional status at study baseline, defined as modified Rankin Scale (mRS; range, 0-5; higher score indicates more disability) score of 0 vs 1 to 2 vs 3 or greater., Main Outcomes and Measures: The primary outcome was recurrent stroke. The secondary outcome was major cardiovascular events (MACE), defined as recurrent stroke, myocardial infarction, new or worsening heart failure, or vascular death., Results: A total of 20 183 PRoFESS participants (mean [SD] age, 66.1 [8.5] years; 12 931 [64.1%] male) and 3265 IRIS participants (mean [SD] age, 62.7 [10.6] years; 2151 [65.9%] male) were included. The median (IQR) follow-up was 2.4 (1.9-3.0) years in PRoFESS and 4.7 (3.2-5.0) years in IRIS. In PRoFESS, the recurrent stroke rate was 7.2%, among patients with an mRS of 0, 8.7% among patients with an mRS of 1 or 2, and 10.6% among patients with an mRS of 3 or greater (χ22 = 27.1; P < .001); in IRIS the recurrent stroke rate was 6.4% among patients with an mRS of 0, 9.0% among patients with an mRS of 1 or 2, and 11.7% among patients with an mRS of 3 or greater (χ22 = 11.1; P < .001). The MACE rate was 10.1% among patients with an mRS of 0, 12.2% among patients with an mRS of 1 or 2, and 17.2% among patients with an mRS of 3 or greater (χ22 = 103.4; P < .001) in PRoFESS and 10.9% among patients with an mRS of 0, 13.3% among patients with an mRS of 1 or 2, and 15.3% among patients with an mRS of 3 or greater (χ22 = 5.8; P = .06) in IRIS. Compared with patients with an mRS of 0, patients with an mRS of 3 or greater had increased hazard for recurrent stroke in PRoFESS (hazard ratio [HR], 1.63; 95% CI, 1.38-1.92; P < .001) and in IRIS (HR, 1.91; 95% CI, 1.28-2.86; P = .002). There was also increased hazard for MACE in PRoFESS (HR, 1.90; 95% CI, 1.66-2.18; P < .001) and in IRIS (HR, 1.45; 95% CI, 1.03-2.03; P = .03)., Conclusions and Relevance: This cohort study found that higher baseline poststroke disability was associated with increased rates of recurrent stroke and MACE. Including more patients with greater baseline disability in stroke prevention trials may improve the statistical power and generalizability of these studies.

Competing Interests: Disclosures Dr Albers reports compensation from Genentech and iSchemaView for consultant services and stock holdings in iSchemaView. Dr Heit reports compensation from Medtronic, iSchemaView, and MicroVention Inc for consultant services. Dr Derdeyn reports grants from Siemens Healthineers and other from Penumbra, Silk Road, NoNo, and Euphrates Vascular outside the submitted work. Dr Inoue reports speaker fees from Bayer, Bristol Myers Squibb, Daichi Sankyo, and Nippon Boehringer Ingelheim. Dr Yedavalli reports consulting fees from MRIOnline and iSchemaView (RapidAI). Dr Seners reports consulting fees for Acticor Biotech. Dr Cereda reports compensation from iSchemaView for consultant services. Dr Mistry serves as a consultant for AbbVie, RAPID AI, and SilverCreek Pharmaceuticals and the American Heart Association. She reports a nonfinancial relationship with Translational Sciences Inc. She reports research funding from the NIH/NINDS and Patient Centered Outcomes Research Institute (PCORI). Dr Chattrerjee reports consulting fees from MDReview and Penumbra Inc. Dr Derdeyn reports Euphrates Vascular - stock options; Silk Road (NITE trial DSMB); Penumbra (MIND and THUNDER trial DSMBs); NoNO (ESCAPE NEXT and FRONTIER DSMBs). Dr Khatri has received a research grant from Cerenovus/Johnson & Johnson (ENDOLOW trial); consulting fees for scientific advisory roles from Lumosa, Basking Biosciences and Shionogi; drug and assays from Translation Sciences (for NIH-funded SISTER trial); royalties from UpToDate (online publication royalties); and funding from NIH STEP Grant (NINDS OT2NS129366). Dr Olivot reports grants from the French Minstry of Health; compensation from Abbvie, Acticor, and Boehringer Ingelheim; and speaker fees from Bristol Myers Squibb. Dr Hill reports grants from Medtronic, Boehringer Ingelheim, NoNO Inc, the Canadian Institutes of Health Research, and MicroVention Inc; compensation from Brainsgate Ltd, for consultant services; a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle NVI; and employment by the University of Calgary. Dr Saver reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson&Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical. Dr Fisher reports compensation from Simcere USA and Lumosa for consultant services; employment by Beth Israel Deaconess Medical Center and Beth Israel Deaconess Medical Center. The other authors report no conflicts.

Background CT perfusion (CTP)-derived baseline ischemic core volume (ICV) can overestimate the true extent of infarction, which may result in exclusion of patients with ischemic stroke from endovascular treatment (EVT). Purpose To determine whether ischemic core overestimation is associated with larger ICV and degree of recanalization. Materials and Methods This retrospective multicenter cohort study included patients with acute ischemic stroke triaged at multimodal CT who underwent EVT between January 2015 and January 2022. The primary outcome was ischemic core overestimation, which was assumed when baseline CTP-derived ICV was larger than the final infarct volume at follow-up imaging. The secondary outcome was functional independence defined as modified Rankin Scale scores of 0-2 90 days after EVT. Successful vessel recanalization was defined as extended Thrombolysis in Cerebral Infarction score of 2b or higher. Categorical variables were compared between patients with ICV of 50 mL or less versus large ICV greater than 50 mL with use of the χ 2 test. Adjusted multivariable logistic regression analyses were used to assess the primary and secondary outcomes. Results In total, 721 patients (median age, 76 years [IQR, 64-83 years]; 371 female) were included, of which 162 (22%) demonstrated ischemic core overestimation. Core overestimation occurred more often in patients with ICV greater than 50 mL versus 50 mL or less (48% vs 16%; P < .001) and those with successful versus unsuccessful vessel recanalization (26% vs 13%; P < .001). In an adjusted model, successful recanalization after EVT (odds ratio [OR], 3.14 [95% CI: 1.65, 5.95]; P < .001) and larger ICV (OR, 1.03 [95% CI: 1.02, 1.04]; P < .001) were independently associated with core overestimation, while the time from symptom onset to imaging showed no association (OR, 0.99; P = .96). Core overestimation was independently associated with functional independence (adjusted OR, 2.83 [95% CI: 1.66, 4.81]; P < .001) after successful recanalization. Conclusion Ischemic core overestimation occurred more frequently in patients presenting with large CTP-derived ICV and successful vessel recanalization compared with those with unsuccessful recanalization. © RSNA, 2024 Supplemental material is available for this article.

Background: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes., Methods: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis., Results: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; P trend <0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; P trend <0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization., Conclusions: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes., Competing Interests: Disclosures Dr Wouters reports grants from Remmert Adriaan-Laan-Fonds. Dr Arquizan reports compensation from Amgen and Medtronic Vascular, Inc, for other services. Dr Christensen reports stock holdings in iSchemaView. Dr Costalat reports compensation from Penumbra, Inc, MicroVention, Inc, Balt USA, LLC, Stryker Corporation, Medtronic USA, Inc, and Johnson & Johnson Health Care Systems, Inc, for consultant services. Dr Heit reports consulting fees from Medtronic and MicroVention, and he is a member of the Medical and Scientific Advisory Board of iSchemaView. Dr Albers reports stock holdings in iSchemaView and compensation from Biogen, iSchemaView, and Genentech for consultant services. The other authors report no conflicts.

Competing Interests: Disclosures Dr Jindal reports service as a chief executive officer at Jindal Neurology, Inc, and is paid per diem as a physician at Kaiser Permanente, South San Francisco, CA. The other authors report no conflicts.

Background: Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters., Methods: We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass., Results: The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min)., Conclusion: BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)