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It is well established that anticoagulation following an ischaemic stroke in the setting of non-valvular atrial fibrillation is an effective means of secondary prevention. However, there is a lack of a solid evidence base to guide both the agent choice and the optimal timing in which to initiate anticoagulation therapy. The decision is complex, and consideration is required to balance the risks between recurrent strokes and potentially causing or exacerbating parenchymal haemorrhages. A clinical audit was performed at a high-volume primary stroke centre looking at anticoagulation prescribing practices among neurologists. We found apixaban was by far the anticoagulation of choice for non-valvular atrial fibrillation. The median time to anticoagulation initiation was Day 1 post transient ischaemic attack, Day 2 post small infarcts, Day 4 post moderate infarcts and Day 5 post large infarcts.

Computed tomography perfusion (CTP) data are important for hyperacute stroke decision making. Available comparisons between outputs of different CTP software packages show variable outcomes. Evaluation for factors associated with agreement between the volume estimates is limited. We assessed for differences in core and penumbra volume estimates of three CTP software packages - AutoMIStar, RAPID, and Vitrea - and analyzed factors associated with agreement between the volume estimates.Differences between software estimates of penumbra and core volumes were calculated for each patient with suspected acute ischemic stroke who underwent CTP. Exploratory hierarchical clustering and principal component analysis were performed to identify factors of decreased volume estimate agreement. Two-sample t-tests were performed, stratified by large vessel occlusion (LVO) location.579 CTP studies were performed; 267 were normal, 139 artifacts, with 172 included in the final analysis. 79/172 had LVO of internal carotid artery (ICA, n = 20), M1 (n = 38) and proximal M2 (n = 21). LVO was the only factor associated with decreased software package agreement, and proximal LVO location was associated with general trend of increasing mean differences and standard deviations between software packages (range of mean differences [SD]: non-LVO, -17-6 [4-33] ml; M2, -40-13 [5-39] ml; M1, -43-26 [16-58] ml; ICA, -76-39 [22-97] ml).Core and penumbra volume estimates can be affected by LVO location significantly between CTP software packages.

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.

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

Ticagrelor is an antiplatelet agent used for treatment of coronary artery disease via inhibition of the P2Y12 receptor. Based on limited literature the safety of intravenous thrombolysis for ischemic stroke in patients with ticagrelor pretreatment is unknown. We present two patients established on ticagrelor treated with intravenous thrombolysis for acute ischemic stroke complicating coronary intervention.

Clinical and imaging characteristics of patients receiving direct oral anticoagulants presenting with transient ischaemic attack or stroke are lacking. A retrospective review of all patients who presented to a high-volume primary stroke centre with acute stroke symptoms while prescribed an oral anticoagulant between January 2012 and June 2017. Clinical, radiological characteristics and functional outcomes were examined. Anticoagulated patients diagnosed with stroke or transient ischaemic attack shared similar disease and outcome characteristics irrespective of anticoagulants used. One-third of warfarin patients with sub-therapeutic international normalised ratios were treated with thrombolytics but no direct oral anticoagulants level was performed in any of the patients, with only one treated by intravenous thrombolysis.

RationaleHaematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.Methods and designStopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.HypothesisIn patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimatesA sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.InterventionParticipants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.Primary efficacy measureThe primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.DiscussionWe describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.

Objectives Computed tomography perfusion (CTP) data are important for hyperacute stroke decision making. Comparisons between outputs of different CTP software packages are limited. We aimed to assess the pair-wise differences in infarct and penumbra estimates produced by three CTP software packages – MIStar, RAPID, and Vitrea. Methods Consecutive patients with suspected acute ischaemic stroke who underwent CTP between July 2020 and June 2021 at our hospital were independently reviewed by two expert readers. Pair-wise differences between software estimates of penumbra and core volumes were calculated for each patient, with analysis stratified by large vessel occlusion (LVO) status (no-LVO, proximal M2, M1 and internal carotid artery-T [ICA-T]). Results 580 CTP studies were performed; 262 were normal, 146 technically poor, with 172 included in the final analysis. 79/172 (45.9%) had LVO; proximal M2 (n=21), M1 (n=38) and ICA-T (n=20). Overall, statistically significant pair-wise differences were seen for both penumbra and core estimates (P Conclusion Core and penumbra volume estimates vary significantly between CTP software packages. There are minimal differences in patients with non-LVO stroke, with the greatest differences seen in patients with ICA-T occlusions.

BACKGROUND AND PURPOSE: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. METHODS: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. RESULTS: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded (

Background and Purpose— Rapid reperfusion with mechanical thrombectomy in ischemic strokes with emergent large vessel occlusions leads to significant reduction in morbidity and mortality. The door-in-door-out (DIDO) time is an important metric for stroke centers without an on-site mechanical thrombectomy service. We report the outcome of a continuous quality improvement program to improve the DIDO time since 2015. Methods— Retrospective analysis of consecutive patients transferred out from a metropolitan primary stroke center for consideration of mechanical thrombectomy between January 1, 2015, and October 31, 2018. Clinical records were interrogated for eligible patients with DIDO times and reasons for treatment delays extracted. Results— One hundred thirty-three patients were transferred over the 46-month period. Median DIDO time reduced by 14% per year, from 111 minutes interquartile range (IQR, 98– 142) in 2015 to 67 minutes (IQR, 55–94) in 2018. A median DIDO time of 59 minutes (IQR, 51–80) was achieved in 2018 during working hours (0800–1700 hours). Overall, 65 patients had no documented delays (49%) with a median DIDO time of 75 minutes (IQR, 54–93) and 103 minutes (IQR, 75–143) in those with at least one delay factor documented. Conclusions— A median DIDO time of

Background and Aims: Disability-adjusted life years (DALYs) are an important measure of the global burden of disease that informs patient outcomes and policy decision-making. Our study aimed to compare the DALYs saved by endovascular thrombectomy (EVT) in the Australasian-based EXTEND-IA trial vs. clinical registry data from EVT in Australian routine clinical practice.Methods: The 3-month modified Rankin scale (mRS) outcome and treatment status of consecutively enrolled Australian patients with large vessel occlusion (LVO) stroke were taken from the International Stroke Perfusion Imaging Registry (INSPIRE). DALYs were calculated as the summation of years of life lost (YLL) due to premature death and years lived with a disability (YLD). A generalized linear model (GLM) with gamma family and log link was used to compare the difference in DALYs for patients receiving/not receiving EVT while controlling for key covariates. Ordered logit regression model was utilized to compare the difference in functional outcome at 3 months between the treatment groups. Cox regression analysis was undertaken to compare the difference in survival over an 18-year time horizon. Estimated long-term DALYs saved based on the EXTEND-IA randomized controlled trial (RCT) results were used as the comparator.Results: INSPIRE patients who received EVT treatment only achieved nominally better functional outcomes than the non-EVT group (p = 0.181) at 3 months. There was no significant survival gain from EVT over the first 3 months of stroke in both INSPIRE and EXTEND-IA patients. However, measured against no EVT in the long-term, EVT in INSPIRE was associated with no significant survival gain [hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.78–1.08, p = 0.287] compared with the survival benefit extrapolated from the EXTEND-IA trial (HR: 0.42, 95% CI: 0.22–0.82, p = 0.01]. Offering EVT to patients with LVO stroke was also associated with fewer DALYs lost (11.04, 95% CI: 10.45–11.62) than those not receiving EVT in INSPIRE (12.13, 95% CI: 11.75–12.51), a reduction of −1.09 DALY (95% CI: −1.76 to −0.43, p = 0.002). The absolute magnitude of the treatment effect was lower than that seen in EXTEND-IA (−2.72 DALY reduction in EVT vs non-EVT patients).Conclusions: EVT for the treatment of LVO in a registry of routine care was associated with significantly lower DALYs lost than medical care alone, but the saved DALYs are less than those reported in clinical trials, as there were major differences in the baseline characteristics of the patients.

Background: Multimodal stroke imaging (Non-contrast CT, CT perfusion and CT angiogram) is essential to acute stroke assessment, there is currently no benchmark for this key process from real world data. Methods: Retrospective review of the turnaround time of consecutive multimodal imaging performed for acute stroke assessment at two high volume stroke centers in Australasia from July to September 2019.Results: 252 imaging studies were included from both sites. The overall median time from acquisition to imaging availability was 13 minutes (IQR 11- 16). The median for Christchurch and Box Hill were 11 minutes (IQR 10 – 12) and 15 minutes (IQR 13 – 19) respectively. Conclusions: Multimodal stroke imaging turnaround time of 11 minutes is a reasonable benchmark.

Background Published reports of acute deterioration during alteplase infusion for acute ischemic stroke due to development of partial to complete large vessel occlusion and collateral failure are sparce. Materials and methods We describe an 84-year-old patient with a fluctuating clinical course due to evolving emergent large vessel occlusion of right M1 segment of the middle cerebral artery and collateral failure during alteplase infusion. Potential mechanisms of acute deterioration within 24 h after thrombolysis are discussed. Results Urgent mechanical thrombectomy was performed with resultant partial recanalization and small volume residual infarcts at 72 h magnetic resonance imaging of brain. Conclusions Progression from partial to complete occlusion may occur within minutes, even during administration of intravenous thrombolytics in hyper-acute stroke. In patients who deteriorate within 24 h of stroke onset, non-contrast CT of brain, followed by CT perfusion and angiography, is the imaging protocol of choice in the mechanical thrombectomy era.

BACKGROUND: Thrombolytic therapy in patients with pre-existing disability presenting with acute ischemic stroke (AIS) is controversial because of concerns regarding poor outcomes and futility of treatment. We hypothesized that a similar proportion of patients with and without pre-existing disability would return to their premorbid functional status following thrombolysis. METHODS: This was a retrospective study at a single high-volume academic primary stroke center. All patients with AIS treated with intravenous alteplase between January 2005 and July 2016 were included. Premorbid functional status was assessed using modified Rankin scale (mRS) and dichotomized as independent premorbid (mRS 0-1) or disabled premorbid (mRS 2-4) groups for comparison. Functional outcome was assessed by mRS at 90 days and compared between groups. RESULTS: Six hundred eighty patients independent premorbid (mean age 71.8 ± 13.1 years, 57.9% male) and 140 disabled premorbid (mean age 82.1 ± 8.7 years, 40.7% male) were included. Patients with pre-existing disability were older and had more vascular risk factors and more severe stroke on presentation (P < 0.05). A greater proportion of patients in the disabled premorbid group were dead at 90 days (35.7% versus 12.8%, P < 0.05). At 90 days, among patients with premorbid mRS 0, 1, 2, 3, and 4: 25%, 38%, 32%, 30%, and 25% of them returned to their respective premorbid mRS status. CONCLUSIONS: Irrespective of premorbid functional level, approximately one fourth to one third of thrombolyzed patients had returned to their premorbid functional levels at 90 days. Thrombolytic treatment should be considered in patients with mild-to-moderate pre-existing disability, taking into account the value placed on the chance of a return to premorbid functional status.

This retrospective study assessed the pattern of telemetry usage and rates of atrial fibrillation (AF) detection in the 6 months pre- and post-implementation of stroke unit monitored telemetry; 122/154 (79%) of patients had telemetry prior to implementation of stroke unit based telemetry and 164/194 (85%) in the 5 months post (P = 0.31). The use of stroke unit based telemetry was associated with a small increase of telemetry usage and significant increase in telemetry hours per patient. AF detection was similar during the two study periods.

Background and Purpose— Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods— Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly. Results— Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16–85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW patients: 57% did not have stroke risk factors, 56% who received medical therapy had recurrent stroke (median 12 months, range 0–97), and 72% were ultimately treated with carotid revascularization (50% carotid stenting, 50% carotid endarterectomy). There were no periprocedural complications or recurrent strokes in carotid revascularization patients. Conclusions— CW leads to ischemic stroke in younger patients without conventional stroke risk factors. We found a high stroke recurrence rate in medically managed symptomatic CW patients, whereas carotid revascularization effectively prevented recurrent stroke. Our findings should be interpreted with caution because of risk of publication and reporting bias.

BACKGROUND Differentiation between true acute tandem occlusion involving the extracranial internal carotid artery (ICA) from pseudotandem occlusion with a patent extracranial ICA has important prognostic and therapeutic implications. We explored the utility of perfusion-derived 4-dimensional CT angiogram (4D-CTA) in identifying carotid pseudo-occlusion in a single-center pilot study. METHODS Acute stroke patients with delayed antegrade ICA flow on 4D-CTA despite an apparent tandem occlusion on conventional single-phase CTA were prospectively identified over a 2.5-year period (2013-2015). RESULTS Eight patients were identified. Delayed antegrade intracranial flow from the apparently occluded ICA was detected up to 50 seconds after contrast administration on 4D-CTA. The distal intracranial ICA was the most common site of true occlusion. Reconstruction of the 4D-CTA images required an additional processing time of 2–3 minutes. CONCLUSIONS 4D-CTA is a novel noninvasive technique that can identify carotid pseudo-occlusion in the acute stroke setting. Our preliminary findings suggest that 4D-CTA can be easily incorporated into an existing acute stroke neuroimaging protocol.

OBJECTIVES The National Quality Forum recently endorsed a performance measure for time to intravenous thrombolytic therapy which allows exclusions for circumstances in which fast alteplase treatment may not be possible. However, the frequency and impact of unavoidable patient reasons for long door-to-needle time (DNT), such as need for medical stabilization, are largely unknown in clinical practice. As part of the Hurry Acute Stroke Treatment and Evaluation-2 (HASTE-2) project, we sought to identify patient and systems reasons associated with longer DNT. METHODS From June 2012 to June 2013 we collected data on DNT and potential reasons for delays from 102 consecutive patients presenting directly to the emergency department who were treated with alteplase within 4.5 hours of symptom onset. RESULTS Mean age was 71 years, 56/113 (54%) were women, median NIH Stroke Scale score was 13, and median DNT was 53 minutes. Potential delays were noted in 59/102 (58%), of which 31/102 (31%) were unavoidable patient-related or eligibility reasons. Median DNT was longer when patient-related or eligibility reasons for delay were present (60 minutes) than when absent (45 minutes, p = 0.005). Multivariable modeling showed that need for urgent medical stabilization, presentation with seizure and inability to confirm eligibility were associated with 35%-50% longer DNT times. CONCLUSIONS Up to 31% of patients have delays due to medical or eligibility-related causes that may be legitimate reasons for providing alteplase later than the benchmark time of 60 minutes.

IntroductionIntravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception.Methods and analysisThe Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0–2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design.Ethics and disseminationPatients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.

BACKGROUND AND PURPOSE: Carotid webs may cause recurrent ischemic stroke. We describe the prevalence, demographics, clinical presentation, imaging features, histopathology, and stroke risk associated with this under-recognized lesion. MATERIALS AND METHODS: A carotid web was defined on CTA as a thin intraluminal filling defect along the posterior wall of the carotid bulb just beyond the carotid bifurcation on oblique sagittal section CTA that was seen as a septum on axial CTA. Using a prospective case series from April 2013 to April 2014, we describe the demographics, spectrum of imaging features on CTA, and histopathology of these carotid webs. From a retrospective analysis of patients at our center from May 2012 to April 2013 who had a baseline head and neck CTA followed by a brain MR imaging within 1–2 days of the CTA, we determine the period prevalence of carotid webs and the prevalence of ipsilateral stroke on imaging. RESULTS: In the prospective series, the mean age was 50 years (range, 41–55 years); 5/7 patients were women. Recurrent stroke was seen in 5/7 (71.4%) patients with the carotid web; time to recurrence ranged from 1 to 97 months. Histopathology suggested a high probability of fibromuscular dysplasia. In the retrospective series, carotid webs were seen in 7/576 patients for a hospital-based-period prevalence of 1.2% (95% CI, 0.4%–2.5%). Two of these 7 patients had acute stroke in the vascular territory of the carotid web. CONCLUSIONS: A carotid web may contribute to recurrent ischemic stroke in patients with no other determined stroke mechanism. Intimal variant fibromuscular dysplasia is the pathologic diagnosis in most cases. The prevalence of carotid web is low, while the optimal management strategy remains unknown.

Background and Purpose— Long-term population trends in the early risk of stroke after transient ischemic attack (TIA) are unknown. We hypothesized that there has been an appreciable decline in the risk of stroke after TIA for the last decade. Methods— Population-level cohort study from Victoria, Australia (population 5.6 million), using linked data from hospitals, emergency departments, and death records (2001–2011), with a 2-year clearance period to define incident TIAs. Age-specific rates/1000, yearly incident rate ratios, and age–sex-adjusted risk of stroke after TIA were computed. Results— The mean age of 46 971 patients with TIA was 71 (SD=15), 52% women. In patients ≥65 years, annual TIA rates declined between 2001 and 2011 from 5.8 to 4.8/1000 (men) and from 5.3 to 4.2/1000 (women). Yearly incident rate ratios were 0.97 (95% confidence interval, 0.96–0.98) in men and 0.97 (95% confidence interval, 0.97–0.98) in women. Overall, the 90-day stroke risk was 3.1%. Age–sex-adjusted risk of stroke at 90 days after a TIA decreased by 3% per year (odds ratio for the effect of year, 0.97; 95% confidence interval, 0.95–0.99). Male sex, direct discharge from emergency departments, public hospital care, stroke unit care, and absence of vascular risk factors were associated with a downward yearly trend of stroke within 90 days of TIA. Conclusions— Over the last 10 years, there has been a measurable decline in the 90-day risk of stroke after an incident TIA and overall decline in rates of TIA in Victoria, Australia. These trends may reflect improved primary and secondary prevention efforts for the last decade.

Background and Purpose— The use of thrombolysis in acute minor ischemic stroke (MIS) remains controversial. We sought to determine the safety and efficacy of intravenous tissue-type plasminogen activator (IV-tPA) in acute MIS patients with demonstrable penumbra on computed tomographic perfusion study. Methods— Consecutive MIS patients with National Institutes of Health Stroke Scale ≤3 were identified from a prospective single tertiary-center database over a 4.5-year period (2011–2015). Cases with demonstrable penumbra were analyzed according to treatment received: IV-tPA versus standard stroke-unit care without thrombolysis. Results— Seventy-three patients of 195 acute MIS admissions had a demonstrable penumbra (34 IV-tPA versus 39 standard stroke-unit care). Overall median National Institutes of Health Stroke Scale and premorbid modified Rankin Scale were 2 and 0, respectively. Median age was 73.2 (interquartile range, 67.3–82.8) years. There were no differences in baseline demographics, risk factors, stroke localization and cause, rates of vascular occlusion (38.2% versus 38.5%; P =1.000), or mean penumbral volume (41.3 versus 25.1 mL; P =0.150; IV-tPA versus standard stroke-unit care) between groups. There were no symptomatic intracerebral hemorrhages in either group. Patients treated with IV-tPA were more likely to have an excellent functional outcome at discharge (88.2% versus 53.9%; P =0.002) and 90 days (91.2% versus 71.8%; P =0.042). Ordinal analysis demonstrated a favorable shift in modified Rankin Scale with IV-tPA both at discharge (odds ratio, 5.23; 95% confidence interval, 1.83–12.20) and 90 days (odds ratio, 4.35; 95% confidence interval, 1.77–11.36). Conclusions— In selected MIS patients with demonstrable penumbra on computed tomographic perfusion, IV-tPA is safe and associated with significant improvement in functional outcome at discharge and 90 days.

We read with interest the recent study of Grossberg et al1 on cervical carotid pseudo-occlusion (PO) showing that PO is relatively common in patients with isolated intracranial internal carotid artery occlusion. We are writing to further highlight the clinical relevance of this poorly recognized entity and the need for an alternative noninvasive diagnostic modality for early detection. Misdiagnoses of PO as true occlusions may affect acute clinical decision making in the era of endovascular clot retrieval. When a chronic carotid occlusion is incorrectly suspected, or when a technically challenging procedure too prolonged for timely …

A previously high-functioning woman presents with clinical and CT features of a subacute ischaemic stroke. Her medical history is relevant for refractory giant cell arteritis on long-term high-dose prednisolone and recent commencement of tocilizumab (interleukin-6 monoclonal antibody). The potential for stroke mimic is considered and a magnetic resonance brain scan is requested. She rapidly deteriorates within 24 hours of admission and unexpectantly dies. An autopsy reveals that she has bilateral pulmonary emboli with lower limb deep vein thrombosis and Pseudomonas meningoencephalitis with frank pus on the brain. We discuss the potential risks of immunosuppression and the role of imaging in the diagnosis of stroke.

Introduction: Previous work suggests that early evaluation and treatment may reduce the stroke risk after TIA by up to 80%. These models of care are resource intensive involving same day access to stroke prevention services, often in urban areas. This is not feasible in many settings, especially where large distances and rural populations are concerned. Hypothesis: We hypothesize that implementation of a province-wide, systematic, multifaceted intervention would lower the recurrent stroke rate in Alberta. Methods: This was a prospective quasi-experimental health services research in the province of Alberta involving a population of 4 million living in an area larger than France (660,000 km2). The ASPIRE interventions, implemented over 15 months, involved education to the public and healthcare providers, creation of a triaging algorithm based on clinical symptoms and onset time, and a 24-7 available TIA Hotline for rapid access to stroke expertise. The primary outcome was the 90-day stroke rate tested with an interrupted time-series regression analysis. Stroke outcomes were adjudicated by two stroke neurologists independently with discrepancies resolved by panel. Secondary outcomes were the composite of stroke, myocardial infarction, death, and the individual components from administrative data tested with age-sex adjusted logistic regression analysis. Results: We included 15709 TIA events in 13671 patients. Age-sex adjusted rate (and %) of stroke recurrence was 1.81 per 100,000 (1.85%) pre-implementation and 1.79 (1.65%) post. The primary outcome was neutral (autoregression coefficient 0.13, p-value 0.70). The 90-day mortality was significantly lower post-implementation (OR 0.75, 95%CI 0.60-0.94). There was a trend in decreased composite endpoint of stroke, myocardial infarction, and death (OR 0.88, 95%CI 0.77-1.01). Conclusions: In a population with low stroke recurrence rates, the successful province-wide implementation of the ASPIRE interventions was associated with decreased mortality, but did not significantly change stroke recurrence. Further studies on improving the identification of high-risk patients is necessary.

Background and Purpose— Although cerebral white matter lesions (WMLs), silent infarcts (SIs), and microbleeds (MBs) are individually associated with poorer gait and balance, it is unknown if they interact. We studied the interactions of WML volume with SI and MB on gait and postural stability. Methods— Participants in a population-based study aged 60 to 86 years underwent brain MRI, computerized gait measurement, and a physiological profile assessment of postural stability. Segmentation procedures and standard rating methods were used to measure WML, SI, and MB. Linear regression was used to test interactions between lesions on gait and postural stability, adjusting for age, sex, and total intracranial volume. Results— There were 395 participants (mean age, 72 years; SD, 7.0). SIs were predominantly located in subcortical frontal white matter and in deep gray structures, and MBs were largely lobar. Participants with SI or MB had higher WML volumes than those without ( P P =0.05, respectively). The presence of SI ( P for interaction=0.01) or MB ( P for interaction P for interaction=0.02), but not MB, magnified the adverse association of WML volume with postural stability. Conclusions— Subclinical cerebrovascular lesions are adversely associated with gait and postural stability in older people in a cumulative fashion.

Differentiating hemorrhagic infarct from parenchymal intracerebral hemorrhage can be difficult. The immediate and long-term management of the two conditions are different and hence the importance of accurate diagnosis. Using a series of intracerebral hemorrhage cases presented to our stroke unit, we aim to highlight the clues that may be helpful in distinguishing the two entities. The main clue to the presence of hemorrhagic infarct on computed tomography scan is the topographic distribution of the stroke. Additional imaging modalities such as computed tomography angiogram, perfusion, and magnetic resonance imaging may provide additional information in differentiating hemorrhagic infarct from primary hemorrhages.

Correct identification of symptomatic high-grade internal carotid artery stenosis from low-grade or total chronic occlusion is critical for patient selection for urgent carotid endarterectomy. Carotid pseudo-occlusion is a flow-related artifact on noninvasive imaging that can lead to an incorrect diagnosis of total internal carotid artery occlusion, thereby denying an eligible patient for appropriate surgical treatment. We present an 82-year-old man with a symptomatic critical internal carotid artery, which was detected on time-resolved 4-dimensional computed-tomography angiography, whereas single-phase computed-tomography angiography, magnetic resonance angiography, and Doppler ultrasonography suggested apparent occlusion. To our understanding, the use of 4-dimensional computed-tomography angiography to identify carotid pseudo-occlusion has not been previously reported.

Acute stroke care has highly time-dependent treatments that require teams of personnel to achieve good outcomes. It is estimated that for every minute the middle cerebral artery remains blocked in an ischemic stroke, 1.9 million neurons are lost.1 Reducing the variance and improving door-to-needle (DTN) time for thrombolysis and time from computed tomography (CT)-to-groin puncture for endovascular therapy will improve outcomes for patients with stroke.1–5 Therefore, reducing variance and improving treatment times are critical components for quality assurance efforts in stroke care. Feedback of DTN performance data has been used in quality improvement initiatives for acute stroke treatment.6,7 In a similar manner, we have observed that the first step of simply providing healthcare personnel with their measured metrics is an inducement to improve and work faster. However, the acute stroke performance data need to be presented in manner that is easy to understand, and it should be available through commonly used modalities to facilitate widespread use. ### Background on Information Visualization Information visualization is a discipline in its own right that combines graphical display in static or dynamic form to reveal a new understanding of data. In clinical medicine, novel methods of information visualization can lead to improved clinical outcomes at both the population and individual levels.8 Famously, in the mid-1800s, John Snow was able to isolate a contaminated water-well and show that cholera was water born by mapping the location and frequency of cholera infections in London’s Soho district.9 Florence Nightingale used her rose petal graphic to show the rise in mortality because of hospital-acquired infections during the Crimean war.10 Simplifying clinical concepts into graphics that are easy to understand can provide insight into the causes of poor health outcomes and lead to positive changes. ### Visualizations in Health Care There has been a rise in the use of …

Background: CT Perfusion (CTP) may inform treatment decisions in acute ischemic stroke (AIS). We sought to determine extent of variability with CTP thresholds for infarct core and penumbra and reasons for such variability using an up-to-date systematic review. Methods: Search strategy combined the themes of AIS, perfusion imaging, and CT/MRI. Two independent reviewers screened at all levels; disagreements were settled through consensus. Inclusion criteria were CTP within 24hrs of stroke onset and reported perfusion thresholds for infarct core, penumbra, and/or normal/not at risk tissue for mixed grey/white matter. Study demographics, QUADAS assessment of quality, and mean thresholds of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), relative CBV (rCBV), relative CBF (rCBF), and relative MTT (rMTT) were collected. Thresholds were reported as median mean threshold (interquartile range). Results: The search resulted in a total of 11919 abstracts from EMBASE and MEDLINE. Of these, 711 studies were identified for full-text review, 134 met all eligibility criteria. 29 studies provided thresholds for CTP and were included in the review. For CBF, median mean threshold was 8.64 (7.94-13.92) ml/min/100g for core, 19.1 (17.1-31.9) ml/min/100g for penumbra and 47.4 (35.6-59.1) ml/min/100g for normal/not at risk tissue. For CBV, median mean threshold was 1.0 (0.68-1.88) ml/100g for core, 2.45 (2.0-3.0) ml/100g for penumbra, and 2.65 (2.0-3.3) ml/100g for normal/not at risk tissue. For MTT median mean threshold was 15.6 (15.3-17.7) seconds for core, 10.5 (7.1-46.2) seconds for penumbra, and 3.9 (3.65-4.15) seconds for normal/not at risk tissue. Median mean threshold for rCBF was 29% (22.5%-35.5%) for core. Sufficient TTP and Tmax data were not reported. Overall, quality was highly variable according QUADAS ranging from 20.7% to 93.1% across the 14 variables. Conclusions: Due to heterogeneity of vendor CTP algorithms, follow-up imaging to define infarct core (NCCT, DWI), unknown recanalization times/reperfusion status and differing onset to CT times, CTP thresholds for infarct core and penumbra are highly variable. As such, a single best threshold for core could not be derived from literature.

A 77-year-old man with ischemic cardiomyopathy and an ejection fraction of 25% presents with a recurrent embolic-looking stroke while taking aspirin and clopidogrel for a coronary stent placed 6 months ago. Computed tomographic angiography of the head and neck is unrevealing. Telemetry reveals a normal sinus rhythm. Renal functions are normal. (1) Should one of the newer oral anticoagulant agents be prescribed for this patient? Off-label use of new oral anticoagulants What is the diagnosis? Stroke neurologists make use of inductive reasoning, a probabilistic exercise, to determine stroke mechanism. Where ≥1 possible mechanism exists, we typically adopt the philosophy of Occam’s razor, assuming that 1 mechanism is dominant. The ensuing approach to preventive treatment rationally follows the determination of stroke mechanism. The appearance of an embolic-looking stroke on brain imaging usually implies a wedge-shaped cortical infarct or multiple scattered infarcts in one or multiple arterial territories. Embolic stroke may be of arterial, cardiac or less commonly, venous origin (paradoxical embolism). From the case history, we infer that arteroembolic stroke arising from a ruptured atherosclerotic plaque is less likely given the unrevealing computed tomographic angiogram. We have no immediate evidence of atrial fibrillation (AF), and we assume that the echocardiographic assessment done to determine the low ejection fraction does not show any alternate source …

The utility of intravenous tissue plasminogen activator (IV t-PA) in improving the clinical outcomes after acute ischemic stroke has been well demonstrated in past clinical trials. Though multiple initial small series of endovascular stroke therapy had shown good outcomes as compared to IV t-PA, a similar beneficial effect had not been translated in multiple randomized clinical trials of endovascular stroke therapy. Over the same time, there have been parallel advances in imaging technology and better understanding and utility of the imaging in therapy of acute stroke. In this review, we will discuss the evolution of endovascular stroke therapy followed by a discussion of the key factors that have to be considered during endovascular stroke therapy and directions for future endovascular stroke trials.

Ventricular tachycardia (VT) is the leading cause of sudden death, and the cardiac ryanodine receptor (RyR2) is emerging as an important focus in its pathogenesis. RyR2 mutations have been linked to VT and sudden death, but their precise impacts on channel function remain largely undefined and controversial. We have previously shown that several disease-linked RyR2 mutations in the C-terminal region enhance the sensitivity of the channel to activation by luminal Ca 2+ . Cells expressing these RyR2 mutants display an increased propensity for spontaneous Ca 2+ release under conditions of store Ca 2+ overload, a process we referred to as store overload–induced Ca 2+ release (SOICR). To determine whether common defects exist in disease-linked RyR2 mutations, we characterized 6 more RyR2 mutations from different regions of the channel. Stable inducible HEK293 cell lines expressing Q4201R and I4867M from the C-terminal region, S2246L and R2474S from the central region, and R176Q(T2504M) and L433P from the N-terminal region were generated. All of these cell lines display an enhanced propensity for SOICR. HL-1 cardiac cells transfected with disease-linked RyR2 mutations also exhibit increased SOICR activity. Single channel analyses reveal that disease-linked RyR2 mutations primarily increase the channel sensitivity to luminal, but not to cytosolic, Ca 2+ activation. Moreover, the Ca 2+ dependence of [ 3 H]ryanodine binding to RyR2 wild type and mutants is similar. In contrast to previous reports, we found no evidence that disease-linked RyR2 mutations alter the FKBP12.6–RyR2 interaction. Our data indicate that enhanced SOICR activity and luminal Ca 2+ activation represent common defects of RyR2 mutations associated with VT and sudden death. A mechanistic model for CPVT/ARVD2 is proposed.

Commentary on: Higgins P, Macfarlane PW, Dawson J, et al. Non-invasive cardiac event monitoring to detect atrial fibrillation after ischemic stroke: a randomized, controlled trial. Stroke 2013;44:2525–31.[OpenUrl][1][Abstract/FREE Full Text][2] Atrial fibrillation (AF) is an established risk factor for stroke, and anticoagulation treatment is effective in reducing recurrent stroke risk. Guidelines recommend the use of clinical prediction tools to select patients with AF for anticoagulation therapy. It has long been recognised that paroxysmal AF (PAF) may pose a similar stroke risk to persistent AF, but the association between the duration of PAF and stroke risk remains uncertain. The best method to detect PAF has yet to be conclusively determined.1 ,2 This randomised controlled trial examines whether prolonged, non-invasive cardiac monitoring poststroke is superior to guideline-based standard treatment in PAF detection. The trial assessed the detection of AF in … [1]: {openurl}?query=rft.jtitle%253DStroke%26rft_id%253Dinfo%253Adoi%252F10.1161%252FSTROKEAHA.113.001927%26rft_id%253Dinfo%253Apmid%252F23899913%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=strokeaha&resid=44/9/2525&atom=%2Febmed%2F19%2F4%2F152.atom

CT of the brain is often negative in acute stroke. The absence of changes suggestive of infarction on MRI of the brain in the setting of a recent stroke is unusual. An otherwise fit and well 69-year-old Caucasian man presented to the hospital with a 26-h history of acute mild right hemiparesis. CT brain on arrival showed no abnormality. MRI brain was also normal 3 weeks post stroke with abnormality seen only at 11 weeks. Stroke remains a clinical diagnosis. The time of the stroke must be taken into consideration when interpreting MRI brain images. Infarct may be ‘invisible’ on MRI in the subacute phase of ischaemic stroke.