Search

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.

© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.562 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) and the Dr. C. J. Vaillant Foundation.

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 Failure to reperfuse a cerebral occlusion resulting in a persistent penumbral pattern has not been fully described. Methods We retrospectively reviewed patients with anterior large vessel occlusion who did not receive reperfusion, and underwent repeated perfusion imaging, with baseline imaging 1.2, and mismatch volume > 10 mL on follow-up imaging. Patients were divided into PTM or non-PTM groups. Ischemic core and penumbral volumes were compared between baseline and follow-up imaging between the two groups, and collateral flow status assessed using CT perfusion collateral index. Results A total of 25 patients (14 PTM and 11 non-PTM) were enrolled in the study. Median core volumes increased slightly in the PTM group, from 22 to 36 ml. There was a much greater increase in the non-PTM group, from 57 to 190 ml. Penumbral volumes were stable in the PTM group from a median of 79 ml at baseline to 88 ml at follow-up, whereas penumbra was reduced in the non-PTM group, from 120 to 0 ml. Collateral flow status was also better in the PTM group and the median collateral index was 33% compared with 44% in the non-PTM group (p = 0.043). Conclusion Multiple patients were identified with limited core growth and large penumbra (persistent target mismatch) > 16 h after stroke onset, likely due to more favorable collateral flow.

BackgroundAt least 20% of strokes involve the posterior circulation (PC). Compared to the anterior circulation, posterior circulation infarction (POCI) are frequently misdiagnosed. CT perfusion (CTP) has advanced stroke care by improving diagnostic accuracy and expanding eligibility for acute therapies. Clinical decisions are predicated upon precise estimates of the ischaemic penumbra and infarct core. Current thresholds for defining core and penumbra are based upon studies of anterior circulation stroke. We aimed to define the optimal CTP thresholds for core and penumbra in POCI.MethodsData were analyzed from 331-patients diagnosed with acute POCI enrolled in the International-stroke-perfusion-registry (INSPIRE). Thirty-nine patients with baseline multimodal-CT with occlusion of a large PC-artery and follow up diffusion weighted MRI at 24–48 h were included. Patients were divided into two-groups based on artery-recanalization on follow-up imaging. Patients with no or complete recanalisation were used for penumbral and infarct-core analysis, respectively. A Receiver operating curve (ROC) analysis was used for voxel-based analysis. Optimality was defined as the CTP parameter and threshold which maximized the area-under-the-curve. Linear regression was used for volume based analysis determining the CTP threshold which resulted in the smallest mean volume difference between the acute perfusion lesion and follow up MRI. Subanalysis of PC-regions was performed.ResultsMean transit time (MTT) and delay time (DT) were the best CTP parameters to characterize ischaemic penumbra (AUC = 0.73). Optimal thresholds for penumbra were a DT >1 s and MTT>145%. Delay time (DT) best estimated the infarct core (AUC = 0.74). The optimal core threshold was a DT >1.5 s. The voxel-based analyses indicated CTP was most accurate in the calcarine (Penumbra-AUC = 0.75, Core-AUC = 0.79) and cerebellar regions (Penumbra-AUC = 0.65, Core-AUC = 0.79). For the volume-based analyses, MTT >160% demonstrated best correlation and smallest mean-volume difference between the penumbral estimate and follow-up MRI (R2 = 0.71). MTT >170% resulted in the smallest mean-volume difference between the core estimate and follow-up MRI, but with poor correlation (R2 = 0.11).ConclusionCTP has promising diagnostic utility in POCI. Accuracy of CTP varies by brain region. Optimal thresholds to define penumbra were DT >1 s and MTT >145%. The optimal threshold for core was a DT >1.5 s. However, CTP core volume estimates should be interpreted with caution.

BACKGROUND We developed a prognostic score to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials.. METHODS We used data from the International CVT Consortium. We excluded patients with pre-existent functional dependency. We used logistic regression to predict poor outcome (modified Rankin Scale 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunken using Ridge regression to adjust for optimism in internal validation. RESULTS Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, we derived the SI2 NCAL2 C score utilizing the following components: absence of female Sex-specific risk factor, Intracerebral hemorrhage, Infection of the central nervous system, Neurologic focal deficits, Coma, Age, lower Level of hemoglobin (g/L), higher Level of glucose (mmol/L) at admission, and Cancer. C-statistics were 0.80 (95%CI 0.75-0.84), 0.84 (95%CI 0.80-0.88) and 0.84 (95%CI 0.80-0.88) for the poor outcome, 30 days and 1 year mortality model, respectively. Calibration plots indicated good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

BACKGROUND AND PURPOSE To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population. METHODS We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up. RESULTS dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8��(5-23) months. Patients with dAVF were older (median [IQR] 53��[44-61] vs. 41��[29-53] years; p��30 days: 39% vs. 7%; p��

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

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors. Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11–21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0–2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.

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.

This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MRA are the recommended sequences for the evaluation of patients within the 4.5 hours time window. Multimodal MRI (DWI/PWI), and more recently, CT perfusion, offer reliable surrogate of salvageable penumbra, the target mismatch, which is now currently used as selection criteria for revascularisation treatment in an extended time window. Those sequences may also help the physician for the management of other limited cases when the diagnosis of acute ischemic stroke is difficult. Another approach the DWI/FLAIR mismatch has been proposed to identify among wake-up stroke patients those who have been experiencing an acute ischemic stroke evolving from less than 4.5hrs. Other biomarkers, such as the clot imaging on MRI and CT, help to predict the recanalisation rate after IVT, while the impact of the presence microbleeds on MRI remains to be determined.

Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P

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.

BackgroundThe optimal time to commence anticoagulation in patients with atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA) is unclear, with guidelines differing in recommendations. A limitation of previous studies is the focus on clinically overt stroke, rather than radiologically obvious diffusion-weighted imaging ischaemic lesions. We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1 month in patients commenced on early (MethodsA prospective multicentre, observational cohort study was performed at 11 Australian stroke centres. Clinical and MRI data were collected at baseline and follow-up, with blinded imaging assessment performed by two authors. Timing of commencement of anticoagulation was at the discretion of the treating stroke physician.ResultsWe recruited 276 patients of whom 208 met the eligibility criteria. The average age was 74.2 years (SD±10.63), and 79 (38%) patients were female. Median National Institute of Health Stroke Scale score was 5 (IQR 1–12). Median baseline ischaemic lesion volume was 5 mL (IQR 2–17). There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation ≥4 days after index event (17% vs 8%, p=0.04), but no difference in haemorrhage rates (22% vs 32%, p=0.10). Baseline ischaemic lesion volume of ≤5 mL was less likely to have a new haemorrhage at 1 month (p=0.02). There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of >5 mL, regardless of anticoagulation timing.ConclusionCommencing anticoagulation

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: One-year risk of stroke in transient ischemic attack and minor stroke (TIAMS) managed in secondary care settings has been reported as 5–8%. However, evidence for the outcomes of TIAMS in community care settings is limited.Methods: The INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study was a prospective inception cohort community-based study of patients of 16 general practices in the Hunter–Manning region (New South Wales, Australia). Possible-TIAMS patients were recruited from 2012 to 2016 and followed-up for 12 months post-index event. Adjudication as TIAMS or TIAMS-mimics was by an expert panel. We established 7-days, 90-days, and 1-year risk of stroke, TIA, myocardial infarction (MI), coronary or carotid revascularization procedure and death; and medications use at 24 h post-index event.Results: Of 613 participants (mean age; 70 ± 12 years), 298 (49%) were adjudicated as TIAMS. TIAMS-group participants had ischemic strokes at 7-days, 90-days, and 1-year, at Kaplan-Meier (KM) rates of 1% (95% confidence interval; 0.3, 3.1), 2.1% (0.9, 4.6), and 3.2% (1.7, 6.1), respectively, compared to 0.3, 0.3, and 0.6% of TIAMS-mimic-group participants. At one year, TIAMS-group-participants had twenty-five TIA events (KM rate: 8.8%), two MI events (0.6%), four coronary revascularizations (1.5%), eleven carotid revascularizations (3.9%), and three deaths (1.1%), compared to 1.6, 0.6, 1.0, 0.3, and 0.6% of TIAMS-mimic-group participants. Of 167 TIAMS-group participants who commenced or received enhanced therapies, 95 (57%) were treated within 24 h post-index event. For TIAMS-group participants who commenced or received enhanced therapies, time from symptom onset to treatment was median 9.5 h [IQR 1.8–89.9].Conclusion: One-year risk of stroke in TIAMS participants was lower than reported in previous studies. Early implementation of antiplatelet/anticoagulant therapies may have contributed to the low stroke recurrence.

Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic.Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic.Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67–0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88–0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65–0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73–0.83)Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.

Delays in acute stroke treatment contribute to severe and negative impacts for patients and significant healthcare costs. Variability in clinical care is a contributor to delayed treatment, particularly in rural, regional and remote (RRR) areas. Targeted approaches to improve stroke workflow processes improve outcomes, but numerous challenges exist particularly in RRR settings. Virtual reality (VR) applications can provide immersive and engaging training and overcome some existing training barriers. We recently initiated the TACTICS trial, which is assessing a “package intervention” to support advanced CT imaging and streamlined stroke workflow training. As part of the educational component of the intervention we developed TACTICS VR, a novel VR-based training application to upskill healthcare professionals in optimal stroke workflow processes. In the current manuscript, we describe development of the TACTICS VR platform which includes the VR-based training application, a user-facing website and an automated back-end data analytics portal. TACTICS VR was developed via an extensive and structured scoping and consultation process, to ensure content was evidence-based, represented best-practice and is tailored for the target audience. Further, we report on pilot implementation in 7 Australian hospitals to assess the feasibility of workplace-based VR training. A total of 104 healthcare professionals completed TACTICS VR training. Users indicated a high level of usability, acceptability and utility of TACTICS VR, including aspects of hardware, software design, educational content, training feedback and implementation strategy. Further, users self-reported increased confidence in their ability to make improvements in stroke management after TACTICS VR training (post-training mean ± SD = 4.1 ± 0.6; pre-training = 3.6 ± 0.9; 1 = strongly disagree, 5 = strongly agree). Very few technical issues were identified, supporting the feasibility of this training approach. Thus, we propose that TACTICS VR is a fit-for-purpose, evidence-based training application for stroke workflow optimisation that can be readily deployed on-site in a clinical setting.

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: A telestroke network in Northern New South Wales, Australia has been developed since 2017. We theorized that the telestroke network development would drive a progressive improvement in stroke care metrics over time.Aim: This study aimed to describe changes in acute stroke workflow metrics over time to determine whether they improved with network experience.Methods: We prospectively collected data of patients assessed by telestroke who received multimodal computed tomography (mCT) and were diagnosed with ischemic stroke or transient ischemic attack from January 2017 to July 2019. The period was divided into two phases (phase 1: January 2017 – October 2018 and phase 2: November 2018 – July 2019). We compared median door-to-call, door-to-image, and door-to-decision time between the two phases.Results: We included 433 patients (243 in phase 1 and 190 in phase 2). Each spoke site treated 1.5–5.2 patients per month. There were Door-to-call time (median 39 in phase 1, 35 min in phase 2, p = 0.18), and door-to-decision time (median 81.5 vs. 83 min, p = 0.31) were not improved significantly. Similarly, in the reperfusion therapy subgroup, door-to-call time (median 29 vs. 24.5 min, p = 0.12) and door-to-decision time (median 70.5 vs. 67.5 min, p = 0.75) remained substantially unchanged. Regression analysis showed no association between time in the network and door-to-decision time (coefficient 1.5, p = 0.32).Conclusion: In our telestroke network, acute stroke timing metrics did not improve over time. There is the need for targeted education and training focusing on both stroke reperfusion competencies and the technical aspects of telestroke in areas with limited workforce and high turnover.

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Continuous surveillance of stroke admissions has been conducted in the Hunter region, Australia, over the past two decades. We aimed to describe the trends in incidence rates of hospitalised stroke and case-fatality rates in this region, 2001-2019.From a hospital-based stroke registry, data for admitted adult stroke patients residing in the Hunter region were collected using ICD-10 codes for ischemic and haemorrhagic stroke. Negative binomial regression and logistic regression analysis were used to analyse trends for age-standardised and age-specific incidence rates of hospitalised stroke and 28-day case-fatality rates.A total of 14,662 hospitalisations for stroke in 13,242 individuals were registered. The age-standardised incidence rate declined from 123 per 100,000 population in the 2001-2005 epoch to 96 in the 2016-2019 epoch (mean annual change -2.0%, incidence rate ratio (IRR) = 0.980 [95%CI: 0.976-0.984]). Age-specific analyses identified significant reduction in the group aged 75-84 (1039 per 100,000 population in 2001-2005 to 633 in 2016-2019, annual change -3.5%, IRR= 0.965 [95%CI: 0.960-0.970]). The 28-day case-fatality rates fluctuated over time (18.5% in 2001-2005, 20.8% in 2010-2015, and 17.8% in 2016-2019). Projected population aging suggests annual volume of patients with new stroke will increase by 77% by 2041 if incidence rates remain unchanged at the 2016-2019 level.Although age-standardised hospitalised stroke incidence rates have declined in the Hunter region, the health system will face an increase in stroke hospitalisations related to the aging population.

Aims: Multimodal computed tomography (mCT) (non-contrast CT, CT angiography, and CT perfusion) is not routinely used to assess posterior fossa strokes. We described the area under the curve (AUC) of brain NCCT, WB-CTP automated core-penumbra maps and comprehensive CTP analysis (automated core-penumbra maps and all perfusion maps) for posterior fossa strokes.Methods: We included consecutive patients with signs and symptoms of posterior fossa stroke who underwent acute mCT and follow up magnetic resonance diffusion weighted imaging (DWI). Multimodal CT images were reviewed blindly and independently by two stroke neurologists and area under the receiver operating characteristic curve (AUC) was used to compare imaging modalities.Results: From January 2014 to December 2019, 83 patients presented with symptoms suggestive of posterior fossa strokes and had complete imaging suitable for inclusion (49 posterior fossa strokes and 34 DWI negative patients). For posterior fossa strokes, comprehensive CTP analysis had an AUC of 0.68 vs. 0.62 for automated core-penumbra maps and 0.55 for NCCT. For cerebellar lesions >5 mL, the AUC was 0.87, 0.81, and 0.66, respectively.Conclusion: Comprehensive CTP analysis increases the detection of posterior fossa lesions compared to NCCT and should be implemented as part of the routine imaging assessment in posterior fossa strokes.

[Background] Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage., [Aim] To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage., [Methods] We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. 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 enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1–3) vs. 2 (1–3) 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 higher bleeding risk.

Background: Transient ischemic attack (TIA) and minor stroke (TIAMS) are risk factors for stroke recurrence. Some TIAMS may be preventable by appropriate primary prevention. We aimed to recruit “possible-TIAMS” patients in the INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study. Methods: A prospective inception cohort study performed across 16 Hunter–Manning region, Australia, general practices in the catchment of one secondary-care acute neurovascular clinic. Possible-TIAMS patients were recruited from August 2012 to August 2016. We describe the baseline demographics, risk factors and pre-event medications of participating patients. Results: There were 613 participants (mean age; 69 ± 12 years, 335 women), and 604 (99%) were Caucasian. Hypertension was the most common risk factor (69%) followed by hyperlipidemia (52%), diabetes mellitus (17%), atrial fibrillation (AF) (17%), prior TIA (13%) or stroke (10%). Eighty-nine (36%) of the 249 participants taking antiplatelet therapy had no known history of cardiovascular morbidity. Of 102 participants with known AF, 91 (89%) had a CHA2DS2-VASc score ≥ 2 but only 47 (46%) were taking anticoagulation therapy. Among 304 participants taking an antiplatelet or anticoagulant agent, 30 (10%) had stopped taking these in the month prior to the index event. Conclusion: This study provides the first contemporary data on TIAMS or TIAMS-mimics in Australia. Community and health provider education is required to address the under-use of anticoagulation therapy in patients with known AF, possibly inappropriate use of antiplatelet therapy and possibly inappropriate discontinuation of antiplatelet or anticoagulation therapy.

Background and Purpose: Telestroke aims to increase access to endovascular clot retrieval (ECR) for rural areas. There is limited information on transfer workflow for ECR in rural settings. We sought to describe the transfer metrics for ECR in a rural telestroke network with respect to decision making. Methods: A retrospective cohort study was employed on consecutive patients transferred to the comprehensive stroke center (CSC) for ECR in a rural hub-and-spoke telestroke network between April 2013 and October 2019, by road or air. Key time-based metrics were analyzed. Results: Sixty-two patients were included. Mean age was 66 years [standard deviation (SD), 14] and median National Institutes of Health Stroke Scale 13 [interquartile range (IQR), 8-18]. Median rural-hospital-door-to-CSC-door (D2D) was 308 min (IQR, 254-351), of which 68% was spent at rural hospitals [door-in-door-out (DIDO); 214 min; IQR, 171-247]. DIDO was longer for air transfers than road (P = 0.004), primarily because of a median 87 min greater decision-to-departure time (Decision-DO, P < 0.001). In multiple linear regression analysis, intubation but not thrombolysis was associated with significantly longer DIDO. The distance at which the extra speed of an aircraft made up for the delays involved in booking an aircraft was 299 km from the CSC. Conclusions: DIDO is longer for air retrievals compared with road. Decision-DO represents the most important component of DIDO, being longer for air transfers. Systems for rapid transportation of rural ECR candidates need optimization for best patient outcomes, with decision support seen as a potential tool to achieve this.

Background: Admission outside normal business hours has been associated with prolonged door-to-treatment times and poorer patient outcomes, the so called “weekend effect. ” This is the first examination of the weekend effect in a telestroke service that uses multi-modal computed tomography. Aims: To examine differences in workflow and triage between in-hours and out-of-hours calls to a telestroke service. Methods: All patients assessed using the Northern New South Wales (N-NSW) telestroke service from April 2013 to January 2019 were eligible for inclusion (674 in total; 539 with complete data). The primary outcomes measured were differences between in-hours and out-of-hours in door-to-call-to-decision-to-needle times, differences in the proportion of patients confirmed to have strokes or of patients selected for reperfusion therapies or patients with a modified Rankin Score (mRS ≤ 2) at 90 days. Results: There were no significant differences between in-hours and out-of-hours in any of the measured times, nor in the proportions of patients confirmed to have strokes (67.6 and 69.6%, respectively, p = 0.93); selected for reperfusion therapies (22.7 and 22.6%, respectively, p = 0.56); or independent at 3 months (34.8 and 33.6%, respectively, p = 0.770). There were significant differences in times between individual hospitals, and patient presentation more than 4.5 h after symptom onset was associated with slower times (21 minute delay in door-to-call, p = 0.002 and 22 min delay in door-to-image, p = 0.001). Conclusions: The weekend effect is not evident in the Northern NSW telestroke network experience, though this study did identify some opportunities for improvement in the delivery of acute stroke therapies.

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.

The original version of this article unfortunately contained mistakes. The correct information is given below.

[Rationale] More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success., [Hypothesis] We hypothesize that individual patient plasmin potential, as measured by in vitro response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early., [Methods] This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after in-vitro addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders., [Outcomes] The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study., [Discussion] If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients., This study was funded by competitive grants from the Australian National Health and Medical Research Council (Reference APP1085550).

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.

Telestroke services have been shown to increase stroke therapy access in rural areas. The implementation of advanced CT imaging for patient assessment may improve patient selection and detection of stroke mimics in conjunction with telestroke. We implemented a telestroke service supported by multimodal CT imaging in a rural hospital in Australia. Over 21 months we conducted an evaluation of service activation, thrombolysis rates and use of multimodal imaging to assess the feasibility of the service. Rates of symptomatic intracranial haemorrhage and 90-day modified Rankin Score were used as safety outcomes. Fifty-eight patients were assessed using telestroke, of which 41 were regarded to be acute ischemic strokes and 17 to be stroke mimics on clinical grounds. Of the 41 acute stroke patients, 22 patients were deemed eligible for thrombolysis. Using multimodal CT imaging, 8 more patients were excluded from treatment because of lack of treatment target. Multimodal imaging failed to be obtained in one patient. For the 14 treated patients, median door-imaging time was 38 min. Median door-treatment time was 91 min. A 90-day mRS ⩽2 was achieved in 40% of treated patients. We conclude that a telestroke service using advanced CT imaging for therapy decision assistance can be successfully implemented in regional Australia and can be used to guide acute stroke treatment decision-making and improve access to thrombolytic therapy. Efficiency and safety is comparable to established telestroke services.

Imaging protocols for acute ischemic stroke varies significantly from center to center leading to challenges in research translation. We aimed to assess the inter-rater reliability of collateral grading systems derived from dynamic computed tomography angiography (CTA) and an optimized multiphase CTA and, to analyze the association of the two CTA modalities with CT perfusion (CTP) compartments by comparing the accuracy of dynamic CTA (dCTA) and optimized multiphase CTA (omCTA) in identifying CT perfusion (CTP) target mismatch patients. Acute ischemic stroke patients with a proximal large vessel occlusion who underwent whole brain CTP were included in the study. Collateral status were assessed using ASPECTS collaterals (Alberta Stroke Program Early CT Score on Collaterals) and ASITN/SIR collateral system (the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology) on dCTA and omCTA. Eighty-one patients were assessed, with a median ischemic core volume of 29 mL. The collateral assessment with ASPECTS collaterals using dCTA have a similar inter-rater agreement (K-alpha: 0.71) compared to omCTA (K-alpha: 0.69). However, the agreement between dCTA and CTP in classifying patients with target mismatch was higher compared to omCTA (Kappa, dCTA: 0.81; omCTA: 0.64). We found dCTA was more accurate than omCTA in identifying target mismatch patients with proximal large vessel occlusion.

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 assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT)., [Methods] In a retrospective, multicenter, blinded, case-control study of patients with recent onset (, [Results] We enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74–0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74–0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8–0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70–0.81)., [Conclusion] Semiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT., [Classification of evidence] This study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT.

Background In stroke survivors, post-stroke fatigue predicts dependency in daily living and failure to return to work. Modafinil shows promise as a pharmacotherapy to reduce post-stroke fatigue and related sequelae, e.g., poorer functional and clinical outcomes. Aims This study explored the cost-effectiveness of modafinil in treating post-stroke fatigue in the Australian context, by determining its incremental cost-effectiveness ratio (ICER) and by simulating the potential cost-savings on a national scale, through a re-analysis of MIDAS trial data. Methods A post hoc cost-effectiveness analysis was undertaken. Part A: patient-level cost and health effect data (Multidimensional Fatigue Inventory (MFI) scores) were derived from the MIDAS trial and analysis undertaken from a health-system perspective. Part B: a secondary analysis simulated the societal impact of modafinil therapy in terms of national productivity costs. Results Part A: Mean cost of modafinil treatment was AUD$3.60/day/patient for a minimally clinically important change (10 points) in total MFI fatigue score, i.e., AUD$0.36/day/unit change in fatigue score per patient. For the base case scenario, the ICER of using modafinil (versus placebo) was AUD$131.73 ($90.17 – 248.15, for minimum and maximum costs, respectively). Part B: The potential productivity cost-savings to society were calculated as nearly AUD$467 million over 1 year, and up to $383,471,991,248 over 10 years, from the widespread use of modafinil treatment in the Australian population of working-age stroke-survivors, representing a significant societal benefit. Conclusions Modafinil is a highly cost-effective treatment for post-stroke fatigue, offering significant productivity gains and potential cost-savings to society from the widespread use of modafinil treatment in the Australian population of working-age stroke-survivors.

Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke. Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset. Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7-16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges. Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.

Background and purposeGiven the promising performance of the new Embolus Retriever with Interlinked Cages (ERIC) in smaller case series, we sought to assess the efficacy and safety of mechanical thrombectomy (MT) with ERIC compared with other stent retrievers (SRs) in acute ischemic stroke due to large vessel occlusion (LVO).MethodsWe reviewed the databases of two comprehensive stroke centers in in Germany and Switzerland for MT due to LVO in the anterior circulation with either ERIC or another SR as a first device. Co-primary outcome was defined as successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) after the first device and favorable outcome (modified Rankin Scale score 0–2) at 90 days' follow-up. Multiple logistic regression analysis was applied to adjust for potential confounders.Results183 consecutive patients with stroke were treated with either ERIC (49%) or a SR (51%) as the first device and successful recanalization was seen in 82% and 57%, respectively (PConclusionThe use of ERIC as a first device appeared to be associated with higher rates of successful recanalization and resulted in better functional outcome. However, favorable outcome was not attributable to ERIC. Most importantly, both device types complemented one another and improved final recanalization rates when used successively.

BackgroundIntracranial atherosclerotic disease is a well-known cause of ischemic stroke. Following the SAMMPRIS trial, medical treatment is favored over stenting. Drug-eluting balloons (DEB) are widely used in coronary angioplasty, showing better results than bare-surface balloons. There is little evidence of DEB employment in intracranial stenosis, especially of paclitaxel-eluted balloons (pDEB). The Neuro Elutax SV (Aachen Resonance) is the first CE certificated pDEB for intracranial use.ObjectiveTo compare pDEB Neuro Elutax SV (ElutaxDEB) with the Wingspan/Gateway stent system (WingspanStent).Materials and methodsA single-center, open-label, retrospective cohort study of 19 patients with symptomatic atherosclerotic intracranial high-grade stenosis treated with either ElutaxDEB or WingspanStent from a tertiary stroke center in Switzerland.ResultsEight patients (42%) received ElutaxDEB. Median clinical follow-up was 10 months for the WingspanStent and 9.5 months for ElutaxDEB (P=0.36). No differences were found in the clinical baseline characteristics, with a median stenosis grade of 80% for the WingspanStent and 81% for the ElutaxDEB (P=0.87). The compound endpoint ‘ischemic re-event and/or restenosis’ was significantly lower for ElutaxDEB (13% vs 64%; P=0.03, OR 0.08 (95% CI 0.007 to 0.93; P=0.043) than for the WingspanStent.ConclusionsThe ElutaxDEB may be a promising alternative treatment for patients with symptomatic high-grade intracranial stenosis showing a significantly lower rate of ischemic re-events or restenosis in comparison with the WingspanStent-treated patients with a similar safety profile. Further studies will be needed to definitively elucidate the role of pDEB in the management of symptomatic intracranial high-grade stenosis.

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.

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

Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy. Aims We aimed to assess the accuracy of an existing 8-item stroke scale (National Institutes of Health Stroke Scale-8 [NIHSS-8]) for identification of patients with acute stroke with LVO. Methods We retrospectively calculated NIHSS-8 scores in a population of consecutive patients with presumed acute stroke assessed by emergency medical services (EMS). LVO was identified on admission computed tomography angiography. Accuracy to identify LVO was calculated using receiver operating characteristics analysis. We used weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS-8 score between the EMS and the hospital stroke team on a prospectively evaluated subgroup. Results Of the 551 included patients, 381 had a confirmed ischemic stroke and 136 patients had an LVO. NIHSS scores were significantly higher in patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score reliably predicted the presence of LVO (area under the receiver operating characteristic curve .82). The optimum NIHSS-8 cutoff of 8 or more had a sensitivity of .81, specificity of .75, and Youden index of .56 for prediction of LVO. The EMS and the stroke team reached substantial agreement (κ = .69). Conclusions Accuracy of the NIHSS-8 to identify LVO in a population of patients with suspected acute stroke is comparable to existing prehospital stroke scales. The scale can be performed by EMS with reasonable reliability. Further validation in the field is needed to assess accuracy of the scale to identify patients with LVO eligible for endovascular treatment in a prehospital setting.

IntroductionThrombolysis with recombinant tissue-type plasminogen activator (rt-PA) fails in more than 60% of patients with acute ischaemic stroke (AIS). Simultaneously, there are risks associated with the use of rt-PA, including the risk of symptomatic intracranial haemorrhage (sICH) even in patients who do re-canalise. While thrombus location, aetiology and infarct size can affect the likelihood of successful thrombolysis, other factors distinguishing patients who re-canalise from those who don’t have yet to be fully elucidated. The ability of rt-PA to promote thrombolysis is dependent upon its capacity to generate plasmin, and we set out to test this capacity ex-vivo. We hypothesised that patients with low plasmin generating capacity are less likely to re-canalise following rt-PA treatment.MethodsPlasma was obtained from 90 AIS patients up to 1 hour before thrombolysis and screened for baseline levels of plasminogen, anti-plasmin, and plasmin-anti-plasmin (PAP) complexes. The degree of inducible plasmin generation was determined using amidolytic assays following ex-vivo addition of rt-PA for 1 hour. ELISA assays were also used to quantitate the fold-increase in PAP complex levels after rt-PA treatment.Resultsrt-PA inducible PAP levels, a surrogate for the capacity to generate plasmin from plasminogen, varied dramatically between patients. The ratio of post-thrombolysis PAP to pre-thrombolysis PAP ranged from 3.4 to 105.9 within the cohort examined for this study. Multivariate regression analyses revealed that each fold increase in PAP levels was associated with a 4.2% increase in the odds of recanalisation (p=0,035) when corrected for blood glucose levels.ConclusionThis is the first report of ex vivo-inducible plasmin generation as a predictor of thrombolysis. The predictive power of this screening assay for sICH is still under investigation.