Expanding the Treatable Imaging Profile in Patients With Large Ischemic Stroke: Subanalysis From a Randomized Clinical Trial
Abstract
BACKGROUND:
We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes.
METHODS:
This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0–3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed.
RESULTS:
Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65–160) mL in patients with EVT and 115 (71–141) mL in the medical management group (P=0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80–223] mL versus 211 [123–289] mL in the medical management group; P<0.001).
CONCLUSIONS:
In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT.
REGISTRATION:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413.
Graphical Abstract
Endovascular thrombectomy (EVT) in patients with large acute ischemic stroke for large vessel occlusion has been established.1–4 A malignant imaging profile is typically associated with a core volume of up to 70 mL5; however, current practice frequently exceeds this threshold with EVT. Despite its widespread use for patient selection, the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) lacks accuracy in assessing ischemic core volume yet remains the standard in numerous studies.6–8 A SELECT study (Secondary Analysis of the Optimizing Patient’s Selection for Endovascular Treatment in Acute Stroke)9 revealed that EVT yielded superior functional outcomes compared with medical intervention when the ischemic core volume measured ≥50 mL on computed tomography perfusion (CTP). In this study, patients with core volumes within the range of 50 to 100 mL had reasonable rates of achieving functional independence post-EVT, whereas those with volumes over 100 mL generally did not achieve independence. Thus, a malignant imaging profile was defined as a volume that led to a modified Rankin Scale (mRS) score of 5 to 6 at 90 days after reperfusion therapy, which was currently thought to be the upper treatable limit. More recently, the ANGEL-ASPECT study (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core) reported that the odds ratio for a favorable mRS shift was 1.40 (1.06–1.85); P=0.01 in patients with ASPECTS of 3 to 5 and core volumes of <70 mL, but only 1.22 (0.81–1.83); P=0.23 in patients with ASPECTS of 3 to 5 and core volumes of ≥70 mL. These findings underline the potential benefit of considering the ischemic core volume when selecting candidates for EVT. Another pooled analysis using diffusion-weighted magnetic resonance imaging (DWI-MRI) demonstrated that ischemic core volumes between 70 and 100 mL may benefit from EVT.10
In the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial), DWI core volumes were also collected in available cases since most of the cases were MRI-based in this trial. This substudy aimed to evaluate the effective boundary of core volume that benefits from EVT.
METHODS
Participants and Study Design
This is a prespecified subanalysis of the RESCUE-Japan LIMIT, which was conducted in 45 Japanese hospitals from November 2018 to December 2021. The study enrolled patients with large vessel occlusion who were treated with EVT and medical management (MM; EVT group), as compared with MM alone (MM group), both having a National Institutes of Health Stroke Scale (NIHSS) score of >6 at the onset. All patients received either noncontrast computed tomography (CT) and CT angiography or DWI-MRI and magnetic resonance angiography (MRA) for evaluating the ASPECTS scoring valued in the range of 3 to 5 as the imaging inclusion criteria. To analyze the quantitative core volume, RAPID software (iSchemaView, Menlo Park, CA) was used for automated determination. DWI cases with calculable core volumes were included in this analysis from both groups. We had 174 DWI cases, of which 6 were not automatically assessable because their b0 did not align with b1000. The data that support the findings of this study are available from the corresponding author upon reasonable request. This study followed the CONSORT (Consolidated Standards of Reporting Trials) reporting guidelines. The study is registered with ClinicalTrials.gov (NCT03702413).
Study Treatments and Interventions
The main study enrolled patients of any sex, including (1) acute ischemic stroke; (2) age ≥18 years; (3) NIHSS score ≥6 on admission; (4) premorbid mRS score of 0 to 1; (5) vessel occlusion at the internal carotid artery or proximal middle cerebral artery segment by CT angiography or MRA; (6) randomization completed within 6 hours from the time when the patient was last known well or up to 24 hours with no ischemic change on fluid-attenuated inversion recovery (FLAIR) imaging known as the DWI-FLAIR mismatch11; (7) EVT initiated within 60 minutes of randomization; and (8) patient or a legally authorized representative signed the informed consent form. Patients were excluded if they had (1) a significant brain mass effect with midline shift in CT or MRI scans; (2) acute intracranial hemorrhage (ICH) in CT or MRI; (3) a high risk of having hemorrhage; or (4) other conditions for which enrollment would not be adequate.
All endovascular procedures were performed by the Japanese Society for Neuroendovascular Therapy-certified neurointerventionalists, basically according to the American Heart Association/American Stroke Association Guideline12 and the Japanese Guidelines for Neuroendovascular Mechanical Thrombectomy.13 All devices used for EVT were approved by Pharmaceuticals and Medical Devices in this study. Recanalization status was classified by the modified Thrombolysis in Cerebral Infarction scale, with successful/complete recanalization defined as modified Thrombolysis in Cerebral Infarction scale score of 2b/3. MM included intravenous thrombolysis with the standard Japanese intravenous thrombolysis protocol.14 The protocol and consent forms were approved by the institutional review boards of Hyogo College of Medicine (No. 3015) and each participating center. All patients or their legally authorized representatives provided written informed consent before randomization.
Imaging Analysis
MRI scans were conducted using conventional 1.5T or 3.0T systems. The MRI protocol comprised baseline DWI and MRA, followed by FLAIR and gradient-echo T2* scans at 48 hours, and FLAIR and MRA on day 7. MRA was performed using the 3-dimensional time-of-flight method to encompass the territory of the Willis artery ring centrally. All DWI images underwent retrospective postprocessing using an automated system (RAPID). The ischemic core lesion was automatically quantified on b0/b1000 MR images, with an apparent diffusion coefficient threshold set at <620×10−6 mm2/s. Final infarct volume was assessed using FLAIR images on day 7, by which time they were attainable. Manual measurements were conducted using MIPAV software (https://mipav.cit.nih.gov/), with absolute infarct growth (mL) also calculated.
Outcomes
The primary outcome was to evaluate the quantitatively measured core volume, which identified functional clinical outcomes (mRS score, 0–3 at 90 days) by the predictive marginal probabilities among both the EVT and MM groups. The intersected values of 95% CI in the marginal plot were estimated as the limit of the boundary volume. Clinical characteristics and radiological values were compared between the groups, considering favorable outcomes (mRS score, 0–2 at 90 days), functional outcomes (mRS score, 0–3 at 90 days), the occurrence of symptomatic intracranial hemorrhages, and mortality within 90 days as safety outcomes. Symptomatic intracranial hemorrhage was defined according to the European Cooperative Acute Stroke Study II criteria (any intracranial hemorrhage with a ≥4-point increase in the NIHSS score from baseline).15
Optimal Thresholds for Outcomes
In addition to estimating the maximum volume for benefit based on the predictive marginal probabilities, we also assessed 3 prespecified thresholds that have been evaluated in prior studies: 70, 100, and 150 mL.2 Because of the exploratory nature of the subanalysis, we aimed to adjust odd ratios by age and sex (a known covariate) if there were significant differences in the demographics. NIHSS was not considered a covariate as it is known to correlate with core volumes. The subgroup analyses assessed the odds of whether the EVT group would have better functional recovery at 90 days in mRS score of 0 to 3 than patients assigned to the MM group.
Dichotomized Thresholds for Outcomes
Patient characteristics and odds ratio for mRS score of 0 to 3 at 90 days were assessed between groups dichotomized by the achieved boundary volume from the predictive marginal probabilities. The correlation test was also performed between core volumes and ASPECTS.
Comparison of the Final Infarct Volume
We also assessed the differences between 2 groups that underwent 7-day follow-up imaging with FLAIR to estimate the final infarct volume and the absolute volume growth.
Statistical Analyses
For describing the study population and comparing 2 groups, we reported percentages for categorical, means and SDs for parametric, and medians and interquartile ranges for nonparametric variables. The χ2, Student t test, and Mann-Whitney U test were used for comparison. The rationale for using predictive marginal probabilities for estimation in our data set stems from the limited population size of patients with large cores, combined with the fact that multivariable logistic regression methods often yield imprecise estimates for small target populations. Marginal probabilities are preferred for inference with categorical confounders and common outcomes.16 The Breslow-Day test of homogeneity was used to compare the odd ratios. All reported P values were 2-tailed, and P<0.05 were considered statistically significant. All analyses were performed using statistical analysis performed with SPSS (IBM SPSS v27; Chicago, IL) and Stata (Stata Corp LP, v15.1, TX). All authors have full access to all the data in the study and take responsibility for its integrity and the data analysis.
RESULTS
Patient Characteristics
Of the 203 cases enrolled, 1 patient withdrew consent, and 202 were included in the original study. Among these patients, 174 (86%) were evaluated for ASPECTS on DWI (DWI-ASPECTS) and 28 on noncontrast CT. Of these, 6 DWI cases were not enrolled because adequate images were missing for automated calculation (no b=0 images). In total, 168 patients (85 in the EVT group versus 83 in the MM group) had a measurable DWI core volume using the RAPID software (Figure 1). The demographic and clinical characteristics of the patients at baseline are shown in Table 1.
| Total (168 cases) | EVT (85 cases) | Medical management (83 cases) | P value | |
|---|---|---|---|---|
| Demographics | ||||
| Female, n (%) | 77 (46) | 40 (47) | 37 (45) | 0.76 |
| Age, y, ±SD | 77±10 | 77±10 | 76±10 | 0.38 |
| Prestroke mRS score, median (IQR) | 0 (0–1) | 0 (0–1) | 0 (0–1) | 0.92 |
| Hypertension, n (%) | 120 (71) | 62 (73) | 58 (70) | 0.73 |
| Diabetes, n (%) | 36 (21) | 20 (24) | 16 (19) | 0.57 |
| Dyslipidemia, n (%) | 42 (25) | 23 (27) | 19 (23) | 0.59 |
| Ischemic heart disease, n (%) | 19 (11) | 13 (15) | 6 (7) | 0.14 |
| Previous stroke, n (%) | 41 (24) | 21 (25) | 20 (24) | 0.72 |
| Current smoker, n (%) | 31 (18) | 14 (16) | 17 (20) | 0.55 |
| Atrial fibrillation, n (%) | 106 (63) | 53 (62) | 53 (64) | 0.87 |
| Median baseline NIHSS score, (IQR) | 22 (18–26) | 22 (18–26) | 22 (17–26) | 0.60 |
| Pathogenic subtype of ischemic stroke | ||||
| Cardioembolic, n (%) | 139 (83) | 73 (86) | 66 (80) | 0.78 |
| Atherothrombosis, n (%) | 9 (5) | 3 (4) | 6 (7) | 0.52 |
| Others, n (%) | 20 (12) | 9 (11) | 11 (13) | 0.77 |
| Use of anticoagulant therapy, n (%) | 36 (21) | 16 (19) | 20 (24) | 0.41 |
| Use of antiplatelet therapy, n (%) | 24 (14) | 13 (15) | 11 (13) | 0.83 |
| Vessel occlusion | ||||
| ICA, n (%) | 80 (48) | 40 (47) | 40 (48) | 1.00 |
| M1, n (%) | 118 (70) | 60 (71) | 58 (70) | 1.00 |
| Tandem lesions, n (%) | 31 (19) | 15 (18) | 16 (19) | 0.84 |
| Time logistics | ||||
| Median time from onset to imaging, min (IQR) | 181 (101–391) | 209 (105–469) | 178 (105–420) | 0.67 |
| Median time from onset to recanalization, min (IQR) | 307 (207–503) | |||
| Radiological characteristic | ||||
| Median core volume, mL (IQR) | 105 (66–146) | 94 (65–160) | 115 (71–141) | 0.72 |
| Median ASPECTS, (IQR) | 3 (3–4) | 3 (3–4) | 3 (3–4) | 0.48 |
| Treatment | ||||
| Intravenous thrombolysis, n (%) | 48 (29) | 25 (29) | 23 (28) | 0.87 |
| Clinical outcomes | ||||
| Functional outcome (mRS, 0–3), n (%) | 40 (24) | 30 (35) | 10 (12) | <0.01 |
| Favorable outcome (mRS, 0–2), n (%) | 19 (11) | 14 (16) | 5 (6) | 0.49 |
| Symptomatic ICH, n (%) | 14 (8) | 9 (11) | 5 (6) | 0.40 |
| Death, n (%) | 36 (21) | 16 (19) | 20 (24) | 0.45 |
| 137 cases† | 72 cases | 65 cases | ||
| Final infarct volume within 14 d, median mL (IQR) | 162 (96–258) | 142 (80–223) | 211 (123–289) | <0.001 |
| Absolute infarct growth from initial core volume, median mL (IQR) | 84 (8–130) | 40 (4–109) | 104 (49–148) | <0.001 |
ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; EVT, endovascular thrombectomy; ICA, internal carotid artery; ICH, intracranial hemorrhage; IQR, interquartile range; M1, proximal middle cerebral artery; mRS, modified Rankin Scale; and NIHSS, National Institutes of Health Stroke Scale.
*
Values are mean (±SD) or median (IQR). Frequencies are numbers (%).
†
Out of 168 cases, 137 cases only remained to have the final images.
Primary Outcome
Predictive marginal probabilities indicated 128 mL as the intersection of the 95% CI of the 2 groups for achieving a favorable outcome, meaning that volumes up to this value are likely to benefit. Additionally, 250 mL represents the intersection of the upper 95% CI for both groups, which may indicate the point at which the estimates converge, suggesting no chance of benefit from EVT in the group (Figure 2). We also analyzed the 90-day outcomes for mRS score of 0 to 2 and found that the data revealed intersections across all core ranges, indicating no significant differences between the 2 therapies (Figure S1). Because we have fewer patients over 128 mL (61 cases, 36%) and 250 mL (5 cases, 3%), the 95% CI was wide, exceeding 1.0. When we dichotomized the population using the 128 mL threshold, a significant difference was observed in clinical outcomes, including mRS score of 0 to 2 as a favorable outcome and 0 to 3 as a functional outcome (Table 2).
| Total (168 cases) | <128 mL (108 cases) | ≥128 mL (60 cases) | P value | |
|---|---|---|---|---|
| Demographics | ||||
| Female, n (%) | 77 (46) | 40 (37) | 31 (52) | 0.34 |
| Age, y, ±SD | 77±10 | 77±10 | 76±9 | 0.35 |
| Prestroke mRS score, median (IQR) | 0 (0–1) | 0 (0–1) | 0 (0–1) | 0.92 |
| Hypertension, n (%) | 120 (71) | 80 (74) | 40 (67) | 0.38 |
| Diabetes, n (%) | 36 (21) | 22 (20) | 14 (23) | 0.70 |
| Dyslipidemia, n (%) | 42 (25) | 30 (28) | 12 (20) | 0.31 |
| Ischemic heart disease, n (%) | 19 (11) | 12 (11) | 7 (12) | 0.96 |
| Previous stroke, n (%) | 41 (24) | 28 (26) | 13 (22) | 0.45 |
| Current smoker, n (%) | 31 (18) | 16 (15) | 15 (25) | 0.25 |
| Atrial fibrillation, n (%) | 106 (63) | 73 (68) | 33 (55) | 0.10 |
| Median baseline NIHSS score, (IQR) | 22 (18–26) | 22 (18–26) | 24 (18–28) | 0.60 |
| Vessel occlusion | ||||
| ICA, n (%) | 80 (48) | 47 (44) | 33 (55) | 0.15 |
| M1, n (%) | 118 (70) | 82 (76) | 36 (60) | 0.07 |
| Time logistics | ||||
| Median time from onset to imaging, minutes (IQR) | 181 (101–391) | 165 (105–405) | 205 (105–625) | 0.37 |
| Median ASPECTS, (IQR) | 3 (3–4) | 3 (3–4) | 3 (3–4) | 0.48 |
| Treatment | ||||
| Intravenous thrombolysis, n (%) | 48 (29) | 38 (35) | 10 (17) | 0.01 |
| Clinical outcomes | ||||
| mRS 0–2 at 90 d, n (%) | 19 (11) | 18 (17) | 1 (2) | <0.01 |
| mRS 0–3 at 90 d, n (%) | 40 (24) | 31 (29) | 9 (15) | 0.02 |
| Symptomatic ICH, n (%) | 14 (8) | 4 (4) | 10 (17) | <0.01 |
| Death, n (%) | 37 (22) | 17 (16) | 20 (33) | <0.01 |
ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; ICA, internal carotid artery; ICH, intracranial hemorrhage; IQR, interquartile range; M1, proximal middle cerebral artery; mRS, modified Rankin Scale; and NIHSS, National Institutes of Health Stroke Scale.
*
Values are mean (±SD) or median (IQR). Frequencies are numbers (%).
Clinical and Safety Outcomes
A significant difference was seen in the EVT group for achieving mRS score of 0 to 3 at 90 days (EVT 35% versus MM 12%; P<0.01) but not in mRS score of 0 to 2 (EVT 16% versus MM 6%; P=0.49). Symptomatic intracranial hemorrhage (EVT 11% versus MM 6%; P=0.40) and death at 90 days (EVT 19% versus MM 24%; P=0.45) had no significant differences (Table 1).
Efficacy of EVT According to Prespecified Core Thresholds
The results among the subgroups with prespecified core thresholds (70, 100, and 150 mL) are shown in Figure 3. The results of the Wilcoxon-Mann-Whitney U test generalized odds ratio for the whole population dichotomized with prespecified core thresholds indicated that the odds of achieving mRS score of 0 to 3 at 90 days were higher for patients with EVT than for patients with MM. When we dichotomized with the volume achieved from the predictive marginal probability (which was 128 mL), patients under this volume had an odds ratio of 5.44 (95% CI, 2.08–14.23) versus 2.08 (95% CI, 0.47–9.19) for the group; however, there were no significant differences (P=0.253; Breslow-Day test of homogeneity for odds ratios; Figure 4). No adjustments were made since no significant difference between the dichotomized groups (by 128 mL) in the baseline characteristics was seen (Table 2).
Final Infarct Volume in Available Patients
Of the 168 cases, 137 had a 7-day follow-up imaging. The 31 cases that could not have a 7-day follow-up imaging were compared and summarized (Table S1), with the most common reason being death before day 7. A final infarct volume was available for 72 patients with EVT and 65 patients with MM. Significant differences were observed in the median (interquartile range) volume (142 [80–223] mL in the EVT group versus 211 [123–289] mL in the MM group; P<0.001). Absolute median (interquartile range) infarct growth also differed between the groups (40 [4–109] mL in the EVT group versus 104 [49–148] mL in the MM group; P<0.001; Figure S2).
DISCUSSION
This analysis emphasizes the impact of ischemic core volumes on both prognosis and the effectiveness of EVT treatment. Patients with ischemic core volumes up to 128 mL showed statistically better outcomes (mRS score, 0–3) with EVT. While previous studies have suggested a treatable range of 70 to 100 mL, our findings indicate that patients with core volumes up to 128 mL, or possibly higher, may still derive significant benefits from EVT, particularly when DWI is used for selection. The original SELECT2 publication suggested no relationship between core volume and treatment response; however, the core volumes reported represented a combination of hypodensity volumes and CTP core volumes, which differed from the statistical analysis plan (see published correction in NEJM). When the SELECT2 were published based on the actual CTP core volumes, patients with core volumes of 100 mL or larger had a numerically lower odds ratio than those with volumes <100 mL.2 The number of patients achieving functional independence with ischemic core volumes exceeding 100 or 150 mL was small, with no clearly defined upper threshold.17
Core Thresholds
The inclusion and exclusion criteria of a trial will determine the enrolled population. Many prior studies have restricted the maximal core volume that can be enrolled and therefore limited the assessment of treatment benefit for large core volumes. For example, several retrospective studies have the suggested benefit of EVT in patients with larger core volumes than 70 mL.18–21 Our study did not have an upper core volume limit; however, patients with DWI ASPECT score of <3 were excluded, which prevented many patients with large core volumes from enrolling. We had a limited number of cases with core volumes above 130 mL and therefore had limited power to determine treatment efficacy or safety for patients with core volumes above 130 mL. Our results indicate that EVT is probably beneficial up to a volume of 128 mL and potentially even higher (refer to Figure 4). In our study, core volume quantification was solely conducted using DWI, while widely used CTP imaging assesses blood flow in injured tissues, and MRI detects restricted diffusion of water molecules due to cytotoxic edema. Consequently, DWI may offer greater accuracy in representing ischemic injury compared with CBF-based CTP assessment, which may underestimate or overestimate the core under certain conditions, particularly in early time windows, among rapid progressors or patients who have early reperfusion.22,23
Core Volumes and ASPECTS Ratings
We have previously reported that among ASPECTS 3 to 5, EVT was not shown to improve the functional outcome at 90 days in patients with ASPECTS 3 compared with ASPECTS 4 and 5.24 When comparing these 2 groups with core volumes (ASPECTS 3 versus 4–5), there was a significant difference (109 mL versus 87 mL; P<0.001), and overall, only moderate correlations were observed between ASPECTS and core volume (ρ=0.467; P<0.001). Looking at ASPECTS, some studies report discrepancies between ASPECTS and core volumes,8 and a recently reported LASTE trial (Large Stroke Therapy Evaluation)25 showed the benefit of EVT in ASPECTS 0 to 5. This study has encouraged treating the extra-low ASPECTS population with EVT, but still, DWI-ASPECTS should be more accurate than ASPECTS ratings to evaluate brain tissue damage by interrater reliability.26
Final Infarct Volume and Infarct Growth Rate Between Treatments
The final infarct volume and absolute infarct growth were significantly smaller in the EVT group (Table 1). This indicates that successful recanalization in EVT can result in minimizing the final core volume and infarct growth. Both final infarct volume and infarct growth are important measurements in assessing the effectiveness of reperfusion therapies. In this regard, we suggest that EVT should be performed in patients with ischemic cores of up to 130 mL to maximize treatment response and minimize the final infarct volume.
Limitations
This study has several limitations. Firstly, the generalization of results is to the East Asian race only. Secondly, the utilization of MRI is relatively rare worldwide. Thirdly, as core volumes increase, the models become less precise and are underpowered, leading to uncertainty in outcomes beyond 128 mL due to limited data availability above this threshold. Predicted marginal probabilities from models may lack independent validation and calibration, as evidenced by our 95% CI exceeding 1.0. Fourthly, although our focus was on the primary outcome of mRS score of 0 to 3, we acknowledge the potential benefit of conducting an mRS shift analysis. However, attempts to perform ordinal regression mRS shift analysis with thresholds of 100 and 150 mL were hindered by insufficient sample sizes for reliable calculation. Fifthly, while this study succeeded in pushing the safely treatable core volume to some extent, it is important to note that patients with large ischemic regions represent high-risk cases, indicating that this is just the beginning of the challenge. An additional limitation is that we did not assess the eloquence of the affected brain areas. Another limitation is the relatively low utilization of intravenous recombinant tissue-type plasminogen activator among the patients enrolled with large ischemic strokes, which may have led to less favorable outcomes in both treatment groups, especially in the medical group. It is imperative to conduct a meta-analysis involving similar large core trials to assess differences in outcomes and modalities such as CT, CTP, and MRI to address these limitations comprehensively.
Conclusions
In this examination of a randomized clinical trial involving patients afflicted with significant ischemic strokes, patients with estimated core volumes up to 128 mL, and potentially larger, may benefit from EVT. As disparities among modalities continue to emerge, there is a growing necessity for a meta-analysis to comprehensively evaluate the advantages of volume assessment.
ARTICLE INFORMATION
Supplemental Material
Figures S1–S2
Table S1
Acknowledgments
The authors would like to express their deepest appreciation to Drs Gregory W. Albers and Michael Mlynash from Stanford University for their support in revising the manuscript and providing statistical advice.
Footnote
Nonstandard Abbreviations and Acronyms
- ASPECTS
- Alberta Stroke Program Early Computed Tomography Score
- CTP
- computed tomography perfusion
- DWI
- diffusion-weighted imaging
- EVT
- endovascular thrombectomy
- FLAIR
- fluid-attenuated inversion recovery
- LASTE
- Large Stroke Therapy Evaluation
- MM
- medical management
- MRA
- magnetic resonance angiography
- MRI
- magnetic resonance imaging
- mRS
- modified Rankin Scale
- NIHSS
- National Institutes of Health Stroke Scale
- RESCUE-Japan LIMIT
- Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial
- SELECT
- Secondary Analysis of the Optimizing Patient’s Selection for Endovascular Treatment in Acute Stroke
Supplemental Material
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Received: 14 February 2024
Revision received: 18 April 2024
Accepted: 24 April 2024
Published online: 28 May 2024
Published in print: July 2024
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Disclosures Dr Inoue reports the lecturer’s fees from Bayer, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim. Dr Yoshimoto reports lecture fees from Takeda Pharmaceutical and Nippon Boehringer Ingelheim. Dr Toyoda reports lecture fees from Bayer, Daiichi Sankyo, Takeda, and Bristol-Myers Squibb. Dr Yamagami discloses research grants from Bristol-Myers Squibb; lecturer’s fees from Stryker, Medtronic, Terumo, Johnson & Johnson, Biomedical Solutions, and Medico’s Hirata; and membership of the advisory boards for Daiichi Sankyo. Dr Sakai reports research grants from Biomedical Solutions, Daiichi Sankyo, and Terumo; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, and Medtronic; and membership on the advisory boards for Johnson & Johnson, Medtronic, and Terumo. Dr Matsumaru reports lecturer fees from Medtronic, Stryker, Terumo, Johnson & Johnson, Kaneka, and Jimro. Dr Matsumoto reports the lecturer’s fees from Kaneka, Medico’s Hirata, Fuji systems, GE Healthcare, Otsuka, Takeda, Century Medical, Terumo, Medtronic, and Stryker. Dr Kimura reports research grants from CSL Behring, Eisai, Kyowa Kirin, Daiichi Sankyo, Teijin, Medtronic, Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Helios; and lecturer’s fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Bayer, Takeda, Medtronic, Otsuka, FP, Alexion, Sanofi, CSL Behring, Novartis, Toa Eiyo, Medico’s Hirata, and Helios. Dr Uchida reports lecturer’s fees from Daiichi Sankyo, Bristol-Myers Squibb, Stryker, and Medtronic. Dr Beppu reports manuscript fees from Medicus Shuppan. Dr Sakakibara reports manuscript fees from Medicus Shuppan. Dr Morimoto reports lecturer’s fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; advisory board for Novartis and Teijin. Dr Yoshimura reports research grants from Medico’s Hirata, Medtronic, and Terumo; and lecturer fees from Medtronic, Kaneka, Stryker, Daiichi Sankyo, Bristol-Meyers Squibb, and Johnson & Johnson. The other author reports no conflicts.
Sources of Funding
This study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion fund of the Japanese Society for Neuroendovascular Therapy. The funding sources did not participate in any part of the study, from conception to article preparation.
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- Beyond the AJR : Investigating the Limits of Mechanical Thrombectomy for Stroke , American Journal of Roentgenology, (1-1), (2025).https://doi.org/10.2214/AJR.24.31849
- Ischaemic brain oedema remains a major unmet need, The Lancet Neurology, 23, 12, (1171-1173), (2024).https://doi.org/10.1016/S1474-4422(24)00439-3
- Intravenous glibenclamide for cerebral oedema after large hemispheric stroke (CHARM): a phase 3, double-blind, placebo-controlled, randomised trial, The Lancet Neurology, 23, 12, (1205-1213), (2024).https://doi.org/10.1016/S1474-4422(24)00425-3
- Glucose and cerebral blood volume index as predictors of ambulatory function for patients presenting with ultra‐large core infarctions, Clinical Neuroimaging, 1, 1-2, (2024).https://doi.org/10.1002/neo2.70007
- Exploring the Limits of Endovascular Therapy for Large Core Patients: Where Do We Need More Data?, Stroke, 55, 7, (1956-1960), (2024)./doi/10.1161/STROKEAHA.124.047228
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