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Background: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0–2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. Methods: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). Results: There were 131 patients; the median age was 64 [53–74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12–22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1–3] versus 3 [1–6] in the patients selected with noncontrast CT+CT angiography, P =0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01–0.19]; P Conclusions: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Background and ObjectivesEndovascular thrombectomy (EVT) is effective for patients with large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined ischemic core. However, the benefit of EVT is unclear in those with a core volume >70 mL. We aimed to compare outcomes of EVT and non-EVT patients with an ischemic core volume ≥70 mL, hypothesizing that there would be a benefit from EVT for fair outcome (3-month modified Rankin scale [mRS] 0–3) after stroke.MethodsA retrospective analysis of patients enrolled into a multicenter (Australia, China, and Canada) registry (2012–2020) who underwent CTP within 24 hours of stroke onset and had a baseline ischemic core volume ≥70 mL was performed. The primary outcome was the estimation of the association of EVT in patients with core volume ≥70 mL and within 70–100 and ≥100 mL subgroups with fair outcome.ResultsOf the 3,283 patients in the registry, 299 had CTP core volume ≥70 mL and 269 complete data (135 had core volume between 70 and 100 mL and 134 had core volume ≥100 mL). EVT was performed in 121 (45%) patients. EVT-treated patients were younger (median 69 vs 75 years; p = 0.011), had lower prestroke mRS, and smaller median core volumes (92 [79–116.5] mL vs 105.5 [85.75–138] mL, p = 0.004). EVT-treated patients had higher odds of achieving fair outcome in adjusted analysis (30% vs 13.9% in the non-EVT group; adjusted odds ratio [aOR] 2.1, 95% CI 1–4.2, p = 0.038). The benefit was seen predominantly in those with 70–100 mL core volume (71/135 [52.6%] EVT-treated), with 54.3% in the EVT-treated vs 21% in the non-EVT group achieving a fair outcome (aOR 2.5, 95% CI 1–6.2, p = 0.005). Of those with a core volume ≥100 mL, 50 of the 134 (37.3%) underwent EVT. Proportions of fair outcome were very low in both groups (8.1% vs 8.7%; p = 0.908).DiscussionWe found a positive association of EVT with the 3-month outcome after stroke in patients with a baseline CTP ischemic core volume 70–100 mL but not in those with core volume ≥100 mL. Randomized data to confirm these findings are required.Classification of EvidenceThis study provides Class III evidence that EVT is associated with better motor outcomes 3 months after CTP-defined ischemic stroke with a core volume of 70–100 mL.

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 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

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.

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 P =0.034), and a lower rate of 3-month poor outcome (12.2% versus 41.4%, P 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 P 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.

Background and Purpose— Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to be an effective agent in reducing poststroke fatigue; however, not all patients reported a significant decrease in fatigue with therapy. We sought to investigate clinical and radiological predictors of fatigue reduction with modafinil therapy in a stroke survivor cohort. Methods— Twenty-six participants with severe fatigue (multidimensional fatigue inventory–20 ≥60) underwent magnetic resonance imaging at baseline and during the last week of a 6-week treatment period of 200 mg modafinil taken daily. Resting-state functional magnetic resonance imaging and high-resolution structural imaging data were obtained, and functional connectivity and regional brain volumes within the fronto-striato-thalamic network were obtained. Linear regression analysis was used to identify predictors of modafinil-induced fatigue reduction. Results— Multiple regression analysis showed that baseline multidimensional fatigue inventory–20 score (β=0.576, P =0.006) and functional connectivity between the dorsolateral prefrontal cortex and the caudate nucleus (β=−0.424, P =0.008) were significant predictors of modafinil-associated decreases in poststroke fatigue (adjusted r 2 =0.52, area under the receiver operator characteristic curve=0.939). Conclusions— Fronto-striato-thalamic functional connectivity predicted modafinil response for poststroke fatigue. Fatigue in other neurological disease has been attributed to altered function of the fronto-striato-thalamic network and may indicate that poststroke fatigue has a similar mechanism to other neurological injury related fatigue. Self-reported fatigue in patients with normal fronto-striato-thalamic functional connectivity may have a different mechanism and require alternate therapeutic approaches. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: ACTRN12615000350527.

Introduction: The fetal-type of the posterior cerebral artery (ftPCA) is a remnant of the embryonic cerebral vasculature and describes a predominant supply of the PCA territory by a branch of the internal carotid artery. It is usually considered a benign anatomical variant with a prevalence ranging between 3% and 40%. Given the larger supply of the brain parenchyma by the anterior circulation in this variant, ftPCA is often associated with a hypoplastic basilar artery and thus a reduced vertebrobasilar blood flow. Hypothesis: Attenuated blood flow through the vertebrobasilar system in patients with a ftPCA is associated with an increased risk of infratentorial ischemic stroke. Methods: We prospectively analyzed 625 consecutive acute stroke patients from our comprehensive stroke center. Cerebral MRI was used to identify stroke location. PCA territory blood supply was classified in 5 subcategories using CT or MRI angiography: 1) total ftPCA (i.e. complete supply via PCOM); 2) predominant ftPCA; 3) balanced PCA (supply via PCOM and P1); 4) predominant P1, and 5) complete P1 supply. Variants 1) and 2) were considered ftPCA for further analysis. We compared the frequencies of anterior, posterior, infratentorial, and multiple territories strokes between patients with and without ftPCA. Results: There were 215 patients (34%) with ftPCA. Patients with ftPCA were significantly more likely to suffer from an infratentorial stroke than those without the ftPCA variant (20% vs 12.2%, P = 0.009). In contrast, anterior, posterior, and multiple territories stroke did not differ between groups. When posterior territory strokes were attributed to the corresponding P1 or PCOM supply, there was no difference in the frequency of vertebrobasilar stroke (i.e. infratentorial plus P1-PCA) between patients with and without ftPCA (P=0.864). Mean cross sectional area of the basilar artery was significantly lower in patients with ftPCA compared to those without ftPCA (6.6mm2 vs. 9.7mm2, P Conclusion: Fetal-type PCA is associated with a higher frequency of infratentorial stroke and a lower cross sectional area of the basilar artery. Possibly, hemodynamic factors influence infratentorial stroke risk in patients with ftPCA.

Objective:To compare the accuracy of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and CT perfusion to detect established infarction in acute anterior circulation stroke.Methods:We performed an observational study in 59 acute anterior circulation ischemic stroke patients who underwent brain noncontrast CT, CT perfusion, and MRI within 100 minutes from CT imaging. ASPECTS scores were calculated by 4 blinded vascular neurologists. The accuracy of ASPECTS and CT perfusion core volume to detect an acute MRI diffusion lesion of ≥70 mL was evaluated using receiver operating characteristics analysis and optimum cutoff values were calculated using Youden J.Results:Median ASPECTS score was 8 (interquartile range [IQR] 5–9). Median CT perfusion core volume was 22 mL (IQR 10.4–71.9). Median MRI diffusion lesion volume was 24.5 mL (IQR 10–63.9). No significant difference was found between the accuracy of CT perfusion and ASPECTS (c statistic 0.95 vs 0.87, p value for difference = 0.17). The optimum ASPECTS cutoff score to detect a diffusion-weighted imaging lesion ≥70 mL was R = 0.88; R2 = 0.77).Conclusions:We found no significant difference between the accuracy of CT perfusion and ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.

Cerebral venous thrombosis is associated with intracranial hemorrhage. The occurrence of brain bleeding complicates management and is associated with worse outcomes. We aimed to identify clinical and imaging risk factors for intracerebral hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracerebral hemorrhage. Methods: We performed a retrospective analysis of an international, multicenter cohort of patients with cerebral venous thrombosis who underwent CT within 2 weeks of symptom onset and who had a subsequent confirmed diagnosis of CVT on MRV, CTV or DSA. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. Results: We recruited 260 patients with cerebral venous thrombosis from 10 institutions in Europe and Mexico. The mean age was 42 and 74% were female. Intracranial hemorrhage was found in 102 (39%). Intracerebral hemorrhage occurred in 64 (63%), small juxtacortical hemorrhage in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Combinations of these types of hemorrhage occurred in 23 (23%). Intraparenchymal hemorrhages in multiple locations occurred in 6 (6%). Older age, presence of hematological disease and superior sagittal thrombosis involvement were significantly associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracerebral hemorrhage (average number of sinuses/veins involved with hemorrhage 2.1 versus 1.9 without hemorrhage, p=0.4). Conclusion: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with the presence of intracranial hemorrhage.

Objective: To compare the predictive capacity to detect established infarct in acute anterior circulation stroke between the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on non-contrast computed tomography (CT) and CT perfusion. Methods: Fifty-nine acute anterior circulation ischemic stroke patients received brain non-contrast CT, CT perfusion and hyperacute magnetic resonance imaging (MRI) within 100 minutes from CT imaging. ASPECTS scores were calculated by 4 independent vascular neurologists, blinded from CT perfusion and MRI data. CT perfusion infarct core volumes were calculated by MIStar software. The accuracy of commonly used ASPECTS cut-off scores and a CT perfusion core volume of ≥ 70 mL to detect a hyperacute MRI diffusion lesion of ≥ 70 ml was evaluated. Results: Median ASPECTS score was 9 (IQR 7-10). Median CT perfusion core volume was 22 ml (IQR 10.4-71.9). Median MRI diffusion lesion volume was 24,5 ml (IQR 10-63.9). ASPECTS score of < 6 had a sensitivity of 0.37, specificity of 0.95 and c-statistic of 0.66 to predict an acute MRI lesion ≥ 70 ml. In comparison, a CT perfusion core lesion of ≥ 70 ml had a sensitivity of 0.76, specificity of 0.98 and c-statistic of 0.92. The CT perfusion core lesion covered a median of 100% of the acute MRI lesion volume (IQR 86-100%). Conclusions: CT perfusion is superior to ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.

Objective: To assess if simplifying a prehospital 8-item NIHSS scale (NIHSS-8, fig 1) to a 0 (symptom absent) – 1 (symptom present) scoring system increases interrater agreement between emergency medical services (EMS) and stroke specialists. Methods: We analysed interrater agreement between EMS and stroke specialists of a single centre on a prospectively collected cohort of 64 suspected acute ischemic stroke patients. EMS performed NIHSS-8 score upon patient arrival at the emergency department. The stroke specialist scored the full 15-item NIHSS blind to the EMS scores and within 5 minutes of patient arrival. Linear-weighted Cohen’s kappa statistics was used to assess agreement between EMS and stroke specialist on the total NIHSS-8 score and each NIHSS-8 scale item. We then simplified each item to a 0-1 score and reassessed interrater agreement for the overall NIHSS-8 scale using linear-weighted Cohen’s kappa statistics and for each NIHSS-8 item using Cohen’s kappa statistics. We used Cohen’s kappa statistics to assess agreement for original and simplified NIHSS-8 cut-off scores. Results: EMS and stroke specialist reached substantial agreement on overall NIHSS-8 scoring (linear-weighted kappa 0.69). Optimum agreement was reached for right arm weakness (linear-weighted kappa 0.79; Table 1) and a cut-off score of 2 and 5 (Cohen’s kappa 0.78; Table 2). When the score was simplified to a 0-1, overall agreement between EMS and stroke specialists was substantial (linear-weighted kappa 0.65). Optimum agreement was seen for LOC questions (Cohen’s kappa 0.78; Table 1) and a cut-off score of 2 (Cohen’s kappa 0.77; Table 2). Conclusion: Simplifying an 8-item prehospital NIHSS stroke scale does not increase interrater agreement between emergency medical services and stroke specialists.

We thank Das et al. and Compagne et al. for the interest in our article.[1][1] An individualized reperfusion treatment approach based on specific imaging profiles will become the standard of care.[2][2],[3][3] Our data indicate that Alberta Stroke Program Early CT Score (ASPECTS) has poorer