Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study.

BACKGROUND: The 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 (<4 days) vs late (≥4 days) anticoagulation. We hypothesised that there would be fewer ischaemic lesions and more haemorrhages in the early anticoagulant group at 1-month MRI. METHODS: A 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. RESULTS: We 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. CONCLUSION: Commencing anticoagulation <4 days after stroke or TIA is associated with fewer ischaemic lesions at 1 month in AF patients. There is no increased rate of haemorrhage with early anticoagulation. These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe, but randomised controlled studies are needed to inform clinical practice.

Automated occlusion detection for the diagnosis of acute ischemic stroke: A detailed performance review.

INTRODUCTION: Stroke is a leading cause of adult disability and death worldwide. Automated detection of stroke on brain imaging has promise in a time critical environment. We present a method for the automated detection of intracranial occlusions on dynamic CT Angiography (CTA) causing acute ischemic stroke. METHODS: We derived dynamic CTA images from CT Perfusion (CTP) data and utilised advanced image processing to enhance and display major cerebral blood vessels for symmetry analysis. We reviewed the performance of the algorithm on a cohort of 207 patients from the International Stroke Perfusion Imaging Registry (INSPIRE), with Large Vessel Occlusion (LVO) and non-LVO strokes. Included in the data were images with chronic stroke, various artefacts, incomplete vessel occlusions, and images of poorer quality. All images were annotated by stroke experts. In addition, each image was graded in terms of the difficulty of the task of occlusion detection. Performance was evaluated on the overall cohort, and with respect to occlusion location, collateral grade, and task difficulty. We also evaluated the impact of including additional perfusion data. RESULTS: Images with a rating of lower difficulty achieved a sensitivity and specificity of 96% and 90%, respectively, while images with a moderate difficulty rating achieved 88% and 50%, respectively. For cases of high difficulty, where more than two experts or additional data were required to reach consensus, sensitivity and specificity was 53% and 11%. The addition of perfusion data to the dCTA images increased the specificity by 38%. CONCLUSION: We have provided an unbiased interpretation of algorithm performance. Further developments include generalising to conventional CTA and employing the algorithm in a clinical setting for prospective studies.

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

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

Video head impulse testing to differentiate vestibular neuritis from posterior circulation stroke in the emergency department: a prospective observational study.

Background and aims: Vertigo is a common presentation to the emergency department (ED) with 5% of presentations due to posterior circulation stroke (PCS). Bedside investigations such as the head impulse test (HIT) are used to risk stratify patients, but interpretation is operator dependent. The video HIT (v-HIT) provides objective measurement of the vestibular-ocular-reflex (VOR) and may improve diagnostic accuracy in acute vestibular syndrome (AVS). We aimed to evaluate the use of v-HIT as an adjunct to clinical assessment to acutely differentiate vestibular neuritis (VN) from PCS. Methods: 133 patients with AVS were consecutively enrolled from the ED of our comprehensive stroke centre between 2018 and 2021. Patient assessment included a targeted vestibular history, HINTs examination (Head Impulse, Nystagmus and Test of Skew), v-HIT and MRI>48 hours after symptom onset. The HINTS/v-HIT findings were analysed and compared between VN, PCS and other cause AVS. Clinical course, v-HIT and MRI findings were used to determine diagnosis. Results: Final diagnosis was VN in 40%, PCS 15%, migraine 16% and other cause AVS 29%. PCS patients were older than VN patients (mean age 68.5±10.6 vs 60.1±14.2 years, p=0.14) and had more cardiovascular risk factors (3 vs 2, p=0.002). Mean VOR gain was reduced (<0.8) in ipsilateral horizontal and (<0.7) anterior canals in VN but was normal in PCS, migraine and other cause AVS. V-HIT combined with HINTs was 89% sensitive and 96% specific for a diagnosis of VN. Conclusions V-HIT combined with HINTs is a reliable tool to exclude PCS in the ED.

Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomised, open-label trial.

BACKGROUND: Mobile stroke units (MSUs) equipped with a CT scanner reduce time to thrombolytic treatment and improve patient outcomes. We tested the hypothesis that tenecteplase administered in an MSU would result in superior reperfusion at hospital arrival, when compared with alteplase. METHODS: The TASTE-A trial is a phase 2, randomised, open-label trial at the Melbourne MSU and five tertiary hospitals in Melbourne, VIC, Australia. Patients (aged ≥18 years) with ischaemic stroke who were eligible for thrombolytic treatment were randomly allocated in the MSU to receive, within 4·5 h of symptom onset, either standard-of-care alteplase (0·9 mg/kg [maximum 90 mg], administered intravenously with 10% as a bolus over 1 min and 90% as an infusion over 1 h), or the investigational product tenecteplase (0·25 mg/kg [maximum 25 mg], administered as an intravenous bolus over 10 s), before being transported to hospital for ongoing care. The primary outcome was the volume of the perfusion lesion on arrival at hospital, assessed by CT-perfusion imaging. Secondary safety outcomes were modified Rankin Scale (mRS) score of 5 or 6 at 90 days, symptomatic intracerebral haemorrhage and any haemorrhage within 36 h, and death at 90 days. Assessors were masked to treatment allocation. Analysis was by intention-to-treat. The trial was registered with ClinicalTrials.gov, NCT04071613, and is completed. FINDINGS: Between June 20, 2019, and Nov 16, 2021, 104 patients were enrolled and randomly allocated to receive either tenecteplase (n=55) or alteplase (n=49). The median age of patients was 73 years (IQR 61-83), and the median NIHSS at baseline was 8 (5-14). On arrival at the hospital, the perfusion lesion volume was significantly smaller with tenecteplase (median 12 mL [IQR 3-28]) than with alteplase (35 mL [18-76]; adjusted incidence rate ratio 0·55, 95% CI 0·37-0·81; p=0·0030). At 90 days, an mRS of 5 or 6 was reported in eight (15%) patients allocated to tenecteplase and ten (20%) patients allocated to alteplase (adjusted odds ratio [aOR] 0·70, 95% CI 0·23-2·16; p=0·54). Five (9%) patients allocated to tenecteplase and five (10%) patients allocated to alteplase died from any cause at 90 days (aOR 1·12, 95% CI 0·26-4·90; p=0·88). No cases of symptomatic intracerebral haemorrhage were reported within 36 h with either treatment. Up to day 90, 13 serious adverse events were noted: five (5%) in patients treated with tenecteplase, and eight (8%) in patients treated with alteplase. INTERPRETATION: Treatment with tenecteplase on the MSU in Melbourne resulted in a superior rate of early reperfusion compared with alteplase, and no safety concerns were noted. This trial provides evidence to support the use of tenecteplase and MSUs in an optimal model of stroke care. FUNDING: Melbourne Academic Centre for Health.

Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit.

INTRODUCTION: Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients' prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase. OBJECTIVE: In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion. METHODS AND ANALYSIS: TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival. ETHICS AND DISSEMINATION: The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences. TRIAL REGISTRATION NUMBER: NCT04071613.

Advanced imaging in acute ischemic stroke: an updated guide to the hub-and-spoke hospitals.

PURPOSE OF REVIEW: The purpose of this review is to summarize the role of the hub-and-spoke system in acute stroke care, highlight the role of advanced imaging and discuss emerging concepts and trials relevant to the hub-and-spoke model. RECENT FINDINGS: The advent of advanced stroke multimodal imaging has provided increased treatment options for patients, particularly in rural and regional areas. When used in the hub-and-spoke model, advanced imaging can help facilitate and triage transfers, appropriately select patients for acute therapy and treat patients who may otherwise be ineligible based on traditional time metrics.Recent, ongoing trials in this area may lead to an even greater range of patients being eligible for acute reperfusion therapy, including mild strokes and patients with large core infarct volumes. SUMMARY: Integration of advanced imaging into a hub-and-spoke system, when complemented with other systems including telemedicine, improves access to acute stroke care for patients in regional and rural areas.

Factors delaying intravenous thrombolytic therapy in acute ischaemic stroke: a systematic review of the literature.

BACKGROUND/AIMS: This review examined factors that delay thrombolysis and what management strategies are currently employed to minimise this delay, with the aim of suggesting future directions to overcome bottlenecks in treatment delivery. METHODS: A systematic review was performed according to PRISMA guidelines. The search strategy included a combination of synonyms and controlled vocabularies from Medical Subject Headings (MeSH) and EmTree covering brain ischemia, cerebrovascular accident, fibrinolytic therapy and Alteplase. The search was conducted using Medline (OVID), Embase (OVID), PubMed and Cochrane Library databases using truncations and Boolean operators. The literature search excluded review articles, trial protocols, opinion pieces and case reports. Inclusion criteria were: (1) The article directly related to thrombolysis in ischaemic stroke, and (2) The article examined at least one factor contributing to delay in thrombolytic therapy. RESULTS: One hundred and fifty-two studies were included. Pre-hospital factors resulted in the greatest delay to thrombolysis administration. In-hospital factors relating to assessment, imaging and thrombolysis administration also contributed. Long onset-to-needle times were more common in those with atypical, or less severe, symptoms, the elderly, patients from lower socioeconomic backgrounds, and those living alone. Various strategies currently exist to reduce delays. Processes which have achieved the greatest improvements in time to thrombolysis are those which integrate out-of-hospital and in-hospital processes, such as the Helsinki model. CONCLUSION: Further integrated processes are required to maximise patient benefit from thrombolysis. Expansion of community education to incorporate less common symptoms and provision of alert pagers for patients may provide further reduction in thrombolysis times.

Patterns of Infarction on MRI in Patients With Acute Ischemic Stroke and Cardio-Embolism: A Systematic Review and Meta-Analysis.

Background: Cardioembolic strokes are common however atrial fibrillation, the most common cause, is often asymptomatic and difficult to detect. There is evidence that infarct topography and volume on magnetic resonance imaging may be associated with specific stroke etiologies. Aim: A systematic review and meta-analysis were undertaken to summarize the available evidence on the association between stroke etiology, infarct topography, and volume. Methods: A systematic review was conducted using Medline (OVID), Embase (OVID), and PubMed databases. Hand searches of the gray literature and of reference lists in relevant articles were also performed. A quality assessment was undertaken, based on the STROBE checklist. For each study, the number of patients with and without a CE source of stroke and infarct topography was collected and outcomes presented as odds ratios (OR) with 95% CI and p-values. Results: Four thousand eight hundred and seventy-three patients with ischemic stroke were included, of whom 1,559 were determined to have a CE source. Bilateral infarcts (OR 3.41; 95% CI 2.20-5.29; p < 0.0001) and multiple territory infarcts (OR 1.57; 95% CI 1.12-2.21; p = 0.009) were more common in patients with a CE source of stroke, than patients without a CE source. Lacunar infarcts (OR 0.49; 95% CI 0.31-0.80; p = 0.004) were more likely to occur in patients without a CE source. No significant difference between the frequency of multiple infarcts (OR 0.96; 95% CI 0.57-1.61; p = 0.87) anterior circulation (OR 1.45; 95% CI 0.83-2.53; p = 0.19) or posterior circulation infarcts (OR 1.06; 95% CI 0.72-1.57; p = 0.75), between the two groups were identified. Three out of four studies examining volume, found a significant association between increased infarct volume and CE source of stroke. A sensitivity analysis with cryptogenic and undetermined stroke sources assumed to be cardioembolic, did not alter the associations observed. Conclusion: The findings of this systematic review and meta-analysis are broadly consistent with previous literature and provide more robust evidence on the association between infarct topography, volume and stroke etiology. Our findings may assist with refining cardiac investigations for patients with cryptogenic stroke, based on infarct topography.

Anticoagulant prescribing in patients with ischaemic stroke: what has changed over a decade?

A study at our institution conducted 10 years ago identified that warfarin was under-utilised in patients with atrial fibrillation. We replicated this study and compared the results. There was a significant increase in the proportion of patients appropriately anticoagulated (63% vs 9%, P < 0.001). Eighty-seven percent of eligible patients were appropriately anticoagulated on discharge (86% previously). Seventy-two percent of treated patients were prescribed a direct oral anticoagulant. Of these, 10% were discharged with a sub-therapeutic dose without obvious explanation.

Management and attitudes toward patients with epilepsy in general practice: How far have we come in three decades?

BACKGROUND: Previous surveys of Australian primary care physicians' attitudes regarding epilepsy and persons with epilepsy (PWE), conducted 20-30 years ago, identified the need for further education in epilepsy care for frontline clinicians. This follow-up study of general practitioners (GPs) in Sydney was conducted to determine the degree of changes in knowledge, attitudes, and management of PWE, with the purpose of evaluating if there had been significant improvement during this period. METHODS: A questionnaire, evaluating various aspects of epilepsy care, including investigations, preferred healthcare provider (HCP), and attitudes toward epilepsy was developed, largely based on the previous work, piloted, and completed by a representative sample of Sydney GPs. RESULTS: A total of 52 completed responses were received. Thirty-six out of 47 GPs (77%) chose neurologists as the most important HCP followed by the GP (9/47; 18.7%). Almost half of the GPs (25/51; 49%) mentioned that they never initiated antiepileptic medication (AEM) therapy by themselves yet half of these GPs would alter the neurologist's regimen, without necessitating referral back to that neurologist. Another 27% (14/51 GPs) rarely commenced AEM therapy. Six out of 50 GPs did not mention an electroencephalogram (EEG) as a routine investigation, and 21/50 did not mention magnetic resonance imaging (MRI) as routine for PWE. The five most commonly used AEMs, identified by at least 10% of respondents, were sodium valproate (42), carbamazepine (37), levetiracetam (31), lamotrigine (16), and phenytoin (15). Emotional, behavioral, and psychosocial issues were perceived to be more common among PWE; however, they could contribute equally well to society as people without epilepsy. CONCLUSION: The results of the study indicate a perceptual shift regarding GP's attitudes to epilepsy; however, there remain deficiencies in knowledge, particularly with regard to investigations and management. The study highlights the need for more formal training of GPs in caring for PWE.

Functional Outcomes at 90 Days in Octogenarians Undergoing Thrombectomy for Acute Ischemic Stroke: A Prospective Cohort Study and Meta-Analysis.

Background: Elderly patients account for 30% of acute ischemic stroke (AIS) but are under-represented in randomized controlled trials of endovascular thrombectomy (EVT). Meta-analysis of "real world" studies evaluating 90-day outcomes in elderly patients ≥80 years have been limited to small numbers undergoing EVT with older generation devices. Methods: A retrospective analysis of 181 prospectively collected patients who received EVT for anterior circulation AIS at an Australian center over 2.5-years. The study aims to determine (i) 90-day functional outcomes (modified Rankin Scale mRS 0-2) in patients ≥80 vs. <80 years, (ii) the interaction of prognostic factors and age and (iii) compare our data to those previously reported using a meta-analysis of outcomes in observational studies using second generation thrombectomy devices. Results: We analyzed 2,387 patients (≥80 years, n = 649; <80 years, n = 1,738) from 14 studies including our study (≥80 years, n = 71; <80 years, n = 110). Twenty-eight percent of our and 30% of the meta-analysis elderly cohort achieved good 90-day mRS compared to 55 and 52%, respectively of younger patients (p < 0.001). Twenty-seven percent of our and 26% of the meta-analysis elderly cohort died compared to 16% (p = 0.07) and 15% (p < 0.0001), respectively of younger patients. Baseline NIHSS≥16 correlated with poor prognosis in elderly (OR 16.4; 95% CI 4.49-59.91, p < 0.001) and younger (OR 8.73;95% CI 3.35-22.80, p < 0.001) patients. Prior rt-PA was associated with favorable outcome in younger (OR 2.90; 95%CI 1.29-6.52, p = 0.01) patients only. Conclusion: EVT has less favorable outcomes in elderly patients. However, results are better than outcomes in historical controls not treated with thrombectomy providing further support for EVT in the elderly.

Subacute Cerebellar Degeneration due to a Paraneoplastic Phenomenon Associated with Metastatic Merkel Cell Carcinoma: A Case Report.

PURPOSE: The aim of this article is to illustrate the diagnostic challenges and management of paraneoplastic neurological syndromes in Merkel cell carcinoma. MATERIALS AND METHODS: We describe a previously functionally independent 85-year-old woman who presented with subacute onset of dizziness and gait ataxia in the setting of metastatic Merkel cell carcinoma. RESULTS: Diagnosis was made on biopsy after positron emission tomography imaging revealed increased metabolic activity in 2 left inguinofemoral lymph nodes. Cerebrospinal fluid analysis was positive for anti-Hu on subsequent admission. Her functional status improved with methylprednisolone treatment and radiotherapy. CONCLUSION: The case highlights the challenge of the evaluation of patients who present with progressive cerebellar signs and the need to consider a paraneoplastic syndrome, especially in the setting of previous malignancy.