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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 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: Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. Methods: Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. Results: During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8–77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9–58.3], P P =0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1–77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5–2.7mL). Conclusions: Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.

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.

Introduction: Anticoagulation reduces recurrent ischemic stroke based on clinical definitions in patients with atrial fibrillation (AF). However, neuroimaging registries suggested a significant proportion developed ischemic lesions on magnetic resonance imaging (MRI) at 12 months follow up. The rate of early recurrent ischemic stroke identified by MRI remains unclear. ATTUNE (Atrial fibrillation in stroke - Utility of Neuroimaging Evaluation) is a prospective, multicentre study of clinical and radiological outcomes in patients commenced on anticoagulation after ischaemic stroke or TIA. We aimed to investigate the incidence of early ischemic stroke on MRI in this group of patients who were anticoagulated. Aims/Methods: We performed an interim analysis of the ATTUNE database to determine the proportion of patients with radiological evidence of infarction and haemorrhage on (MRI), one month after index ischemic stroke or transient ischemic attack (TIA). MRIs performed at one month were analysed independently by two experienced neuroimage assessors and the number of new infarcts and haemorrhages determined for each patient. Results: A total of 216 patients were analysed. The median age was 74 (IQR 68-81). Anticoagulation was commenced a median of 4 days after index event (IQR 2-6). Twenty-eight patients had new infarcts on follow-up MRI (13%). Fifty-six had new haemorrhage on follow up MRI (26%). Of these, 41 patients had hemorrhagic transformation of the initial infarct and 15 had a remote haemorrhage. Conclusion: There is a high rate of recurrent ischemic lesions and haemorrhages on MRI in patients commenced on anticoagulation within 30 days of index stroke or TIA.

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.

Background and Purpose— Low left ventricular ejection fraction (LVEF) leads to worse outcomes after stroke. We hypothesized that the arterial input function (AIF) variability on perfusion computed tomography, especially the time between scan onset and end of AIF (SO-EndAIF), would reflect reduction of cardiac output. Methods— Retrospective analysis of consecutive stroke patients, who underwent computed tomography between January 2013 and September 2018, was performed in 2 parts. (1) To determine the correlation between SO-EndAIF and LVEF, all patients with a transthoracic echocardiogram performed ±6 months from the time of stroke were included. LVEF was dichotomized as either normal (≥50%) or decreased (3 seconds and with clinical outcome measured using 3-month modified Rankin Scale. Results— A total of 732 ischemic stroke patients underwent computed tomography, 231 with transthoracic echocardiogram were included in part (1), 393 with outcome data were included in part (2). In part (1), 193/231 (83.5%) had normal LVEF (median 61%) and 38/231 (16.5%) decreased LVEF (median 39%). The low-LVEF group had significantly prolonged SO-EndAIF compared with normal-LVEF group (mean of 39.7 versus 26 second; P P P P P P =0.033). Conclusions— AIF width correlates with ejection fraction in acute ischemic stroke. A 29-second threshold from scan onset to end of AIF accurately predicts reduced LVEF and identifies patients more likely to have worse outcomes after 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.

Background and Purpose— Transient ischemic attack (TIA) initiates an ischemic cascade without resulting in frank infarction and, as such, represents a novel model to study the effects of this ischemic cascade and secondary neurodegeneration in humans. Methods— Patients with suspected TIA underwent acute brain perfusion imaging, and those with acute ischemia were enrolled into a prospective observational study. We collected baseline and 90-day magnetic resonance imaging, including MP-RAGE (high-resolution T1 sequence) and cognitive assessment with the Montreal Cognitive Assessment. Brain morphometry and within patient statistical analysis were performed to identify changes between baseline and 90-day imaging and clinical assessments. Results— Fifty patients with TIA with acute perfusion lesions were studied. All patients experienced a decrease in global cortical gray matter ( P =0.005). Patients with anterior circulation TIA (n=31) also had a significant reduction in the volume of the pons ( P P P =0.002), frontal lobe ( P P =0.003), and thalamus ( P =0.016). Patients with an anterior perfusion lesion on acute imaging also had a significant decrease in Montreal Cognitive Assessment between baseline and day 90 ( P =0.027), which may be related to the volume of thalamic atrophy ( R 2 =0.28; P =0.009). Conclusions— In a prospective observational study, patients with TIA confirmed by acute perfusion imaging experienced a significant reduction in global gray matter and focal structural atrophy related to the area of acute ischemia. The atrophy also resulted in a proportional decreased cognitive performance on the Montreal Cognitive Assessment. Further studies are required to identify the mechanisms of this atrophy.

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.