CTP-Defined Large Core Is a Better Predictor of Poor Outcome for Endovascular Treatment Than ASPECTS-Defined Large Core.

BACKGROUND: Recent trials confirmed the effectiveness of endovascular therapy in patients with large ischemic cores. Yet the optimal neuroimaging modalities to define large core remains unclear. We tried to address this question by comparing the functional outcomes in patients receiving thrombectomy selected by either noncontrast computed tomography Alberta Stroke Program Early Computed Tomography Score (ASPECTS) or computed tomography perfusion (CTP). METHODS: This study retrospectively selected patients enrolled in the International Stroke Perfusion Registry between August 2011 and April 2022. Patients with acute stroke with large vessel occlusion in anterior circulation treated with endovascular therapy were included. All received both CTP and noncontrast computed tomography. The primary outcome was defined as poor functional outcome represented by a modified Rankin Scale score of 5 to 6 at 3 months. Large cores were defined in terms of either (1) noncontrast computed tomography ASPECTS ≤5 or (2) core volume ≥70 mL on CTP. RESULTS: A total of 1115 patients were included in the analysis, of which 90 patients had ASPECTS ≤5 (8.1%) and 97 patients CTP core ≥70 mL (8.7%). A fair agreement between ASPECTS and CTP with a κ value of 0.31 (0.21-0.40) was found. Compared with patients with neither CTP nor ASPECTS large cores, those with only ASPECTS-defined large cores (ie, ASPECTS ≤5; n=56) did not have a higher adjusted odds of poor outcome (29%; odds ratio, 1.84 [0.91-3.73]; P=0.089). However, patients with CTP large core but not ASPECTS-defined large core (n=63) had a higher adjusted odds of poor outcome (60%; odds ratio, 3.91 [2.01-7.60]; P<0.001). In time-stratified subgroup analysis (>6 versus ≤6 hours), ASPECTS showed no discriminative difference between ≤5 and >5 in poor outcome for patients receiving endovascular therapy within 6 hours. CONCLUSIONS: CTP core ≥70 mL-defined large cores are more predictive of poor outcome than ASPECTS ≤5-defined core in endovascular therapy patients, particularly within 6 hours after stroke onset.

Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV.

We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection - namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels - and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval.

Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial.

BACKGROUND: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). METHODS: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. FINDINGS: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84). INTERPRETATION: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. FUNDING: Australian National Health and Medical Research Council and Stryker USA.

Whole Blood Viscosity and Cerebral Blood Flow in Acute Ischemic Stroke.

Existing effective treatments for ischemic stroke restore blood supply to the ischemic region using thrombolysis or mechanical removal of clot. However, it is increasingly recognized that successful removal of occlusive thrombus from the large artery-recanalization, may not always be accompanied by successful restoration of blood flow to the downstream tissues-reperfusion. Ultimately, brain tissue survival depends on cerebral perfusion, and a functioning microcirculation. Because capillary diameter is often equal to or smaller than an erythrocyte, microcirculation is largely dependent on erythrocyte rheological (hemorheological) factors such as whole blood viscosity (WBV). Several studies in the past have demonstrated elevated WBV in stroke compared with healthy controls. Also, elevated WBV has shown to be an independent risk factor for stroke. Elevated WBV leads to endothelial dysfunction, decreases nitric oxide-dependent flow-mediated vasodilation, and promotes hemostatic alterations/thrombosis, all leading to microcirculation sludging. Compromised microcirculation further leads to decreased cerebral perfusion. Hence, modulating WBV through pharmacological agents might be beneficial to improve cerebral perfusion in stroke. This review discusses the effect of elevated WBV on endothelial function, hemostatic alterations, and thrombosis leading to reduced cerebral perfusion in stroke.

Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies.

OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.

Automated CT Perfusion Detection of the Acute Infarct Core in Ischemic Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: In patients with acute ischemic stroke, the location and volume of an irreversible infarct core determine prognosis and treatment. We aimed to determine if automated CT perfusion (CTP) is non-inferior to diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) in predicting the acute infarct core. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and EMBASE from 1960 to December 2020. Five outcome measures were examined: volumetric difference, volumetric correlation, sensitivity and specificity at the patient level, Dice coefficient, and sensitivity and specificity at the voxel level. A random-effects meta-analysis was performed for volumetric difference and correlation. RESULTS: From 3,986 studies retrieved, 48 studies met our inclusion criteria with 46 studies on anterior circulation, one study on posterior circulation, and one study on lacunar infarct strokes. In anterior circulation stroke, there were no significant mean volumetric differences between CTP and acute DWI (cerebral blood flow [CBF] 0.52 mL, 95% CI [-0.07, 1.11], I2 0.0%; relative CBF [rCBF] 3.01 mL, 95% CI [-0.46, 6.48], I2 82.6%; relative cerebral blood volume [rCBV] -12.84 mL, 95% CI [-38.56, 12.88], I2 96.2%) and between CTP and delayed DWI or FLAIR (rCBF -1.29 mL, 95% CI [-6.49, 3.92], I2 91.8%; rCBV -5.80 mL, 95% CI [-16.20, 4.60], I2 84.2%). Mean correlation between CTP and acute DWI was 0.90 (95% CI [0.80, 0.95], I2 60.0%) for rCBF and 0.84 (95% CI [0.58, 0.94], I2 93.5%) for rCBV. Mean correlation between CTP and delayed DWI or FLAIR was 0.74 (95% CI [0.57, 0.85], I2 94.6%) for rCBF and 0.90 (95% CI [0.69, 0.97], I2 93.1%) for rCBV. Sensitivity and specificity at the patient level were reported by three studies and Dice coefficient by four studies. Statistical analysis could not be performed for sensitivity and specificity at the voxel level. Limited evidence was available for posterior circulation or lacunar infarct strokes. CONCLUSION: Due to significant heterogeneity and insufficient high-quality studies reporting each outcome, there is insufficient evidence to reliably determine the accuracy of CTP prediction of the infarct core compared to DWI or FLAIR.

Modelling the Long-Term Health Outcome and Costs of Thrombectomy in Treating Stroke Patients with Large Ischaemic Core: Comparison between Clinical Trials and Real-World Data.

INTRODUCTION: We aimed to assess the long-term health outcomes and costs of endovascular thrombectomy (EVT) using clinical trials and real-world evidence in patients with large ischaemic core. METHODS: Both clinical trials and the INternational Stroke Perfusion Imaging REgistry (INSPIRE) were used. Patients with acute computed tomography perfusion scan with an ischaemic core of ≥70 mL were included. A Markov model was constructed to simulate the long-term costs and health outcomes (quality-adjusted life year) post-index stroke. Effectiveness of EVT (modified Rankin scale score at 3 months) was derived from the trials and INSPIRE registry (compared to matched patients not treated with EVT), respectively. RESULTS: Based on the trial and real-world data, the overall results revealed varied health benefits and costs due to EVT, with reduced health benefits and increased costs from EVT treatment in everyday practice. The long-term simulation estimated that offering EVT to large vessel occlusion stroke patients with large ischaemic core was associated with greater benefits (1.12 vs. 0.25 quality-adjusted life year gains) and lower (-A$19,320) or higher costs (A$11,278), using trial and real-world data, respectively. The incremental cost of the EVT procedure (i.e., A$14,356) could be primarily offset to a different extent by the reduction in costs related to the nursing home care (-$31,986 vs. -A$1,874) in the clinical trial and real-world practice. CONCLUSIONS: Our results highlight the potential gaps when implementing an effective intervention in the real world and the importance of the rigorous selection of large infarct core patients for EVT.

Cost-Effectiveness of Endovascular Thrombectomy in M2 Occlusion Stroke: Real-World Experience Versus Clinical Trials.

OBJECTIVES: This study sought to establish the cost-effectiveness of endovascular thrombectomy (EVT) in M2 occlusions compared with patients who did not have EVT using both real-world and clinical trial evidence. METHODS: The effectiveness of EVT in M2 occlusions was informed by the International Stroke Perfusion Imaging Registry (INSPIRE, real-world data for a wide range of strokes) and HERMES collaboration, trial data. Patients who received EVT and non-EVT treatment from INSPIRE were matched according to baseline characteristics. A Markov model with 7 health states defined by the 3-month modified Rankin scale (mRS) was constructed. Endovascular thrombectomy and non-EVT-treated patients in real-world, and clinical trials were run through the Markov model separately to generate the results from a limited societal perspective. National statistics and published literature informed the long-term probability of recurrent stroke, mortality, costs of management post-stroke, non-medical care, and nursing home care. RESULTS: A total of 83 (42 EVT and 41 non-EVT) patients were matched of 278 (45 EVT and 233 non-EVT) patients in INSPIRE who had M2 occlusion stroke at presentation. The long-term simulation estimated that offering EVT to M2 occlusion stroke patients was associated with greater benefits (5.48 EVT vs 5.24 non-EVT quality-adjusted life year [QALY]) and higher costs (A$133 457 EVT vs A$126 127 non-EVT) compared with non-EVT treatment in real-world from a limited societal perspective. The incremental cost-effectiveness ratio (ICER) of EVT in real-world was A$29 981 (€19 488)/QALY. The analysis using the data from HERMES collaboration yielded consistent results for the EVT patients. Comparison with real-world cost-effectiveness analyses of EVT in internal carotid artery/middle cerebral artery-M1 (ICA/MCA-M1) occlusion suggested a potential reduced QALY gains and increased ICER in M2 occlusions. CONCLUSIONS: Our study suggested that the benefits gained from EVT in M2 occlusion stroke in the real-world were similar to that derived from the clinical trials. The clinical and cost benefits from EVT appeared to be reduced in M2 compared with that from the ICA/MCA-M1 occlusions. CLINICAL IMPACT: Our study has provided valuable insights into the clinical significance of endovascular therapy (EVT) in the context of M2 occlusion stroke within a real-world setting. It is noteworthy that our findings indicate that the benefits obtained from EVT in M2 occlusion stroke closely align with those observed in controlled clinical trials. However, it is essential to recognize that there is a reduction in the clinical and cost-related advantages when comparing M2 occlusions to more proximal ICA/MCA-M1 occlusions.

CT vascular territory mapping: a novel method to identify large vessel occlusion collateral.

INTRODUCTION: This descriptive study explores typical patterns of vascular territory mapping (VTM) in ischaemic stroke patients with proximal vessel occlusion. VTM is a novel process using CT perfusion that can identify the source and extent of collateral blood flow in patients with vessel occlusion. It functions by determining which vessel provides dominant blood flow to a brain voxel. METHODS: A total of 167 consecutive patients were analysed from INSPIRE (International Stroke Perfusion Imaging Registry) with their CT perfusion reprocessed through VTM software. We explored the typical territory maps generated by this software relating to common large vessel occlusion location sites (ACA/MCA/PCA). RESULTS/CONCLUSION: In the presence of occlusion, VTM demonstrated a reciprocal increase in collateral vessel territories.

Comparison of Computed Tomography Perfusion and Multiphase Computed Tomography Angiogram in Predicting Clinical Outcomes in Endovascular Thrombectomy.

BACKGROUND: In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes. METHODS: We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital. All patients underwent CTP for endovascular thrombectomy, and the mCTA collateral score was determined using CTP-reconstructed mCTA images. The primary outcome was 90-day functional outcomes defined by modified Rankin Scale. Multivariable logistic regression models analyzed associations between mCTA and CTP parameters and 90-day functional outcomes. The ability to discriminate 90 days-functional outcomes was compared between mCTA collateral score and CTP parameters using receiver operating curve analysis and C statistics. RESULTS: One hundred and twenty patients were included. The median age was 69 years (interquartile range, 60-79), the median baseline National Institutes of Health Stroke Scale score was 14 (interquartile range, 9-19). The baseline ischemic core volume, defined by CTP-based relative cerebral blood flow <30%, was associated with excellent functional outcome (modified Rankin Scale score 0-1; odds ratio, 0.942 [-0.897 to -0.989]; P=0.015) and poor functional outcome (modified Rankin Scale score 5-6; odds ratio, 1.032 [1.007-1.056]; P=0.010) at 90 days in the analysis of multivariable regression. There was no significant association between the mCTA score and excellent functional outcome (P=0.58) or poor functional outcome (P=0.155). The relative cerebral blood flow <30%-based regression model best fit the data for the 90-day poor functional outcome (C statistic, 0.834). CONCLUSIONS: The CTP-based ischemic core volume may provide better discrimination for 90-day functional outcomes for patients with acute stroke undergoing endovascular thrombectomy than the mCTA collateral score.

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke.

Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.

Optimal Tissue Reperfusion Estimation by Computed Tomography Perfusion Post-Thrombectomy in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b is defined as successful reperfusion. However, mTICI has rarely been correlated with dynamic perfusion imaging postendovascular therapy for acute stroke. We aimed to study the proportion of tissue optimal reperfusion (TOR) postendovascular therapy across different grades of mTICI. METHODS: We conducted a single-center retrospective analysis of patients with acute ischemic strokes who had endovascular therapy between 2018 and 2019. Computer tomography perfusion or magnetic resonance perfusion was performed before and after endovascular therapy. Tmax+6 volume reduction of >90% was defined as TOR. Comparisons of proportions of TOR in different grades of mTICI were performed. In the present study, the requirement for informed consents was waived. RESULTS: Eighty-two patients were included. The difference in the proportion of TOR for TICI categories was statistically significant (mTICI score 0, 0%, mTICI score 2A, 0%, mTICI score 2b, 50.0%, mTICI score 2c, 80.0%, mTICI score 3, 81.3%, χ2=14.035, P=0.003). Multivariable logistic regression showed that lower age (odds ratio, 0.932, P=0.017), onset-to-tissue-type plasminogen activator time (odds ratio, 0.980, P=0.005) and TOR (odds ratio, 8.764, P=0.031) were associated with favorable functional outcome. CONCLUSIONS: The proportion of TOR achieved by mTICI score of 2b was significantly lower than mTICI score of 2c and mTICI score of 3. TOR was associated with favorable functional outcome, and the degree of reperfusion was more strongly correlated with outcomes than the mTICI scores.

Role of Computed Tomography Perfusion in Identification of Acute Lacunar Stroke Syndromes.

BACKGROUND AND PURPOSE: Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions. METHODS: A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps. RESULTS: We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69). CONCLUSIONS: Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.

Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy.

BACKGROUND AND PURPOSE: This study aimed to explore whether the therapeutic benefit of endovascular thrombectomy (EVT) was mediated by core growth rate. METHODS: This retrospective cohort study identified acute ischemic stroke patients with large vessel occlusion and receiving reperfusion treatment, either EVT or intravenous thrombolysis (IVT), within 4.5 hours of stroke onset. Patients were divided into 2 groups: EVT versus IVT only patients (who had no access to EVT). Core growth rate was estimated by the acute core volume on perfusion computed tomography divided by the time from stroke onset to perfusion computed tomography. The primary clinical outcome was good outcome defined by 3-month modified Rankin Scale score of 0-2. Tissue outcome was the final infarction volume. RESULTS: A total of 806 patients were included, 429 in the EVT group (recanalization rate of 61.6%) and 377 in the IVT only group (recanalization rate of 44.7%). The treatment effect of EVT versus IVT only was mediated by core growth rate, showing a significant interaction between EVT treatment and core growth rate in predicting good clinical outcome (interaction odds ratio=1.03 [1.01-1.05], P=0.007) and final infarct volume (interaction odds ratio=-0.44 [-0.87 to -0.01], P=0.047). For patients with fast core growth of >25 mL/h, EVT treatment (compared with IVT only) increased the odds of good clinical outcome (adjusted odds ratio=3.62 [1.21-10.76], P=0.021) and resulted in smaller final infarction volume (37.5 versus 73.9 mL, P=0.012). For patients with slow core growth of <15 mL/h, there were no significant differences between the EVT and the IVT only group in either good clinical outcome (adjusted odds ratio=1.44 [0.97-2.14], P=0.070) or final infarction volume (22.6 versus 21.9 mL, P=0.551). CONCLUSIONS: Fast core growth was associated with greater benefit from EVT compared with IVT in the early <4.5-hour time window.

Does Intravenous Thrombolysis Within 4.5 to 9 Hours Increase Clot Migration Leading to Endovascular Inaccessibility?

BACKGROUND AND PURPOSE: Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours. METHODS: We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data. Baseline and 12- to 24-hour follow-up clot location was determined on computed tomography angiogram or magnetic resonance angiogram. The incidence of clot migration leading to a change from retrievable to nonretrievable location was identified and compared between the two treatment groups (IVT versus placebo). RESULTS: Two hundred twenty patients were assessed. Clot migration from a retrievable to nonretrievable location occurred in 37 patients: 21 patients (19.3%) in the placebo group and 16 patients (14.4%) in the IVT group. No significant difference was identified in the incidence of clot migration leading to inaccessibility between groups (P=0.336). CONCLUSIONS: Our results did not show increased clot migration leading to clot inaccessibility in patients treated with IVT.

Permeability Measures Predict Hemorrhagic Transformation after Ischemic Stroke.

OBJECTIVE: We sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measures in ischemic stroke patients receiving alteplase only. METHODS: A pixel-based analysis of pretreatment CT perfusion (CTP) was undertaken to define the optimal CTP permeability thresholds to predict the likelihood of HT. We then compared previously proposed predictors of HT using regression analyses and receiver operating characteristic curve analysis to produce an area under the curve (AUC). We compared AUCs using χ2 analysis. RESULTS: From 5 centers, 1,407 patients were included in this study; of these, 282 had HT. The cohort was split into a derivation cohort (1,025, 70% patients) and a validation cohort (382 patients or 30%). The extraction fraction (E) permeability map at a threshold of 30% relative to contralateral had the highest AUC at predicting any HT (derivation AUC 0.85, 95% confidence interval [CI], 0.79-0.91; validation AUC 0.84, 95% CI 0.77-0.91). The AUC improved when permeability was assessed within the acute perfusion lesion for the E maps at a threshold of 30% (derivation AUC 0.91, 95% CI 0.86-0.95; validation AUC 0.89, 95% CI 0.86-0.95). Previously proposed associations with HT and parenchymal hematoma showed lower AUC values than the permeability measure. INTERPRETATION: In this large multicenter study, we have validated a highly accurate measure of HT prediction. This measure might be useful in clinical practice to predict hemorrhagic transformation in ischemic stroke patients before receiving alteplase alone. ANN NEUROL 2020;88:466-476.

Automated estimation of ischemic core prior to thrombectomy: comparison of two current algorithms.

PURPOSE: Endovascular thrombectomy (EVT) improves clinical outcomes in ischemic stroke with large vessel occlusion. Clinical benefits are inversely proportional to size of the pre-treatment ischemic core. This study compared estimated ischemic core volumes by two different CT perfusion (CTP) automated algorithms to the gold standard follow-up infarct volume using diffusion-weighted imaging (DWI) to assess for congruence, and thus eligibility for EVT. METHODS: Retrospective, single-center cohort study of 102 patients presenting to a comprehensive stroke center between 2012 and 2018. Inclusion criteria were CT perfusion prior to EVT, successful EVT with mTIBI 2b-3 reperfusion, and DWI post-EVT. CTP data were retrospectively processed by two algorithms: "delay and dispersion insensitive deconvolution" (DISD, RAPID software) versus "delay and dispersion corrected single value decomposition" (ddSVD, Mistar software), using commercially available software. Core volumes were compared to follow up DWI using independent software (MRIcron). Agreement between each algorithm and DWI was estimated using Lin's concordance coefficient and analyzed using reduced major axis regression. RESULTS: We included 102 patients. Both algorithms had excellent agreement with DWI (Lin's concordance coefficients: DISD 0.8 (95% CI: 0.73; 0.87), ddSVD 0.92 (95% CI: 0.89; 0.95). Compared to ddSVD (reduced major axis slope = 0.95), DISD exhibited a larger extent of proportional bias (slope = 1.12). CONCLUSION: The ddSVD algorithm better correlates with DWI follow-up infarct volume than DISD processing. The DISD algorithm overestimated larger ischemic cores which may lead to patient exclusion from thrombectomy based on selection by core volume.

Physiotherapy using a free-standing robotic exoskeleton for patients with spinal cord injury: a feasibility study.

BACKGROUND: Evidence is emerging for the use of overground lower limb robotic exoskeletons in the rehabilitation of people with spinal cord injury (SCI), with suggested benefits for gait speed, bladder and bowel function, pain management and spasticity. To date, research has focused on devices that require the user to support themselves with a walking aid. This often precludes use by those with severe trunk, postural or upper limb deficits and places the user in a suboptimal, flexed standing position. Free-standing exoskeletons enable people with higher level injuries to exercise in an upright position. This study aimed to evaluate the feasibility of therapy with a free-standing exoskeleton for those with SCI, and to determine the potential health-related benefits of this intervention. METHODS: This 12-week intervention study with 12-week waitlist control and 12-week follow up, provided people with SCI scoring < 5 on the mobility section of the spinal cord independence measure (SCIM-III) twice weekly therapy in the REX (Rex Bionics, Auckland, NZ), a free-standing lower limb robotic exoskeleton. The primary outcome measure of interest was function, as measured on the SCIM-III. A battery of secondary outcomes was included. Participants also completed a survey on their perceptions of this treatment modality, to determine acceptability. RESULTS: Forty-one potential participants were screened for eligibility. Two females (one ASIA A, one ASIA C) and one male (ASIA B) completed all 24 intervention sessions, and the follow up assessment. One participant showed positive trends in function, fatigue, quality of life and mood during the intervention phase. Grip and quadriceps strength, and lower limb motor function improved in another. Two improved their percentage of lean body mass during the intervention phase. Remaining results were varied across patients, time points and outcomes. The intervention was highly acceptable to all participants. CONCLUSION: With three of 41 potential participants being eligible and completing this study, our results show that there are potential benefits of exercise in a free-standing exoskeleton for people with severe mobility impairment due to SCI, for a small subset of patients. Further research is warranted to determine those most likely to benefit, and the type of benefit depending on the patient characteristics. Trial registration The trial was registered prospectively on 20 April 2018 at www.anzctr.org.au/ (ACTRN12618000626268).

Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: This study aimed to evaluate the treatment effect of intraarterial versus intravenous tirofiban during endovascular thrombectomy in acute ischemic stroke. METHODS: This study retrospectively examined 503 patients with acute ischemic stroke with large vessel occlusion who received endovascular thrombectomy within 24 hours of stroke onset. Patients were divided into 3 groups: no tirofiban (n=354), intraarterial tirofiban (n=79), and intravenous tirofiban (n=70). The 3 groups were compared in terms of recanalization rate, symptomatic intracerebral hemorrhage, in-hospital death rate, 3-month death, and 3-month outcomes measured by modified Rankin Scale score (good clinical outcome of 0-2, poor outcome of 5-6). The comparison was statistically assessed by propensity score matching, followed by Freidman rank-sum test and pairwise Wilcoxon signed-rank test with Bonferroni correction. RESULTS: The propensity score matching resulted in 92 matched triplets. Compared with the no-tirofiban group, the intravenous tirofiban group showed significantly increased recanalization (96.7% versus 64.1%, P<0.001), an increased rate of 3-month good outcome (69.5% versus 51.2%, P=0.034), and a lower rate of 3-month poor outcome (12.2% versus 41.4%, P<0.001). There was no significant difference between the tirofiban intravenous and no-tirofiban groups in terms of symptomatic intracerebral hemorrhage (2.2% versus 0%, P=1.000). However, symptomatic intracerebral hemorrhage was significantly increased in the intraarterial-tirofiban group compared with the no-tirofiban group (19.1% versus 0%, P<0.001), with an increased rate of in-hospital death (23.6% versus 0% P<0.001), and increased rate of 3-month death (26.8% versus 11.1%, P=0.021). The intraarterial-tirofiban and no-tirofiban group showed no significant difference in recanalization rate (66.3% versus 64.1%, P=1.000). CONCLUSIONS: As an adjunct to endovascular thrombectomy, intravenous tirofiban is associated with high recanalization rate and good outcome, whereas intraarterial tirofiban is associated with high hemorrhagic rate and death rate.