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Background and Purpose— Basilar artery occlusion is associated with high risk of disability and mortality. This study aimed to assess the prognostic value of a new radiological score: the Basilar Artery on Computed Tomography Angiography (BATMAN) score. Methods— A retrospective analysis of consecutive stroke patients with basilar artery occlusion diagnosed on computed tomographic angiography was performed. BATMAN score is a 10-point computed tomographic angiography–based grading system which incorporates thrombus burden and the presence of collaterals. Reliability was assessed with intraclass coefficient correlation. Good outcome was defined as modified Rankin Scale score of ≤3 at 3 months and successful reperfusion as thrombolysis in cerebral infarction 2b-3. BATMAN score was externally validated and compared with the Posterior Circulation Collateral score. Results— The derivation cohort included 83 patients with 41 in the validation cohort. In receiver operating characteristic (ROC) analysis, BATMAN score had an area under receiver operating characteristic curve of 0.81 (95% confidence interval [CI], 0.7–0.9) in derivation cohort and an area under receiver operating characteristic curve of 0.74 (95% CI, 0.6–0.9) in validation cohort. In logistic regression adjusted for age and clinical severity, BATMAN score of P =0.01), in validation cohort (odds ratio, 6.9; 95% CI, 1.4–33; P =0.01), and in endovascular patients, after adjustment for recanalization and time to treatment (odds ratio, 4.8; 95% CI, 1.2–18; P =0.01). BATMAN score of P =0.04). Conclusions— The addition of collateral quality to clot burden in BATMAN score seems to improve prognostic accuracy in basilar artery occlusion patients.

Objectives: Hospital data used to assess regional variability in disease management and outcomes, including mortality, lack information on disease severity. We describe variance between hospitals in 30-day risk-adjusted mortality rates (RAMRs) for stroke, comparing models that include or exclude stroke severity as a covariate. Design: Cohort design linking Australian Stroke Clinical Registry data with national death registrations. Multivariable models using recommended statistical methods for calculating 30-day RAMRs for hospitals, adjusted for demographic factors, ability to walk on admission, stroke type, and stroke recurrence. Setting: Australian hospitals providing at least 200 episodes of acute stroke care, 2009–2014. Main outcome measures: Hospital RAMRs estimated by different models. Changes in hospital rank order and funnel plots were used to explore variation in hospital-specific 30-day RAMRs; that is, RAMRs more than three standard deviations from the mean. Results: In the 28 hospitals reporting at least 200 episodes of care, there were 16 218 episodes (15 951 patients; median age, 77 years; women, 46%; ischaemic strokes, 79%). RAMRs from models not including stroke severity as a variable ranged between 8% and 20%; RAMRs from models with the best fit, which included ability to walk and stroke recurrence as variables, ranged between 9% and 21%. The rank order of hospitals changed according to the covariates included in the models, particularly for those hospitals with the highest RAMRs. Funnel plots identified significant deviation from the mean overall RAMR for two hospitals, including one with borderline excess mortality. Conclusions: Hospital stroke mortality rates and hospital performance ranking may vary widely according to the covariates included in the statistical analysis.

Background: Given the potential differences in etiology and impact, the treatment and outcome of younger patients (aged 18–64 years) require examination separately to older adults (aged ≥65 years) who experience acute stroke. Methods: Data from the Australian Stroke Clinical Registry (2010–2015) including demographic and clinical characteristics, provision of evidence-based therapies and health-related quality of life (HRQoL) post-stroke was used. Descriptive statistics and multilevel regression models were used for group comparisons. Results: Compared to older patients (age ≥65 years) among 26,220 registrants, 6,526 (25%) younger patients (age 18–64 years) were more often male (63 vs. 51%; p < 0.001), born in Australia (70 vs. 63%; p < 0.001), more often discharged home from acute care (56 vs. 38%; p < 0.001), and less likely to receive antihypertensive medication (61 vs. 73%; p < 0.001). Younger patients had a 74% greater odds of having lower HRQoL compared to an equivalent aged-matched general population (adjusted OR 1.74, 95% CI 1.56–1.93, p < 0.001). Conclusions: Younger stroke patients exhibited distinct differences from their older counterparts with respect to demographic and clinical characteristics, prescription of antihypertensive medications and residual health status.

The aim of acute stroke treatment is to reperfuse the penumbra. However, not all posttreatment reperfusion is associated with a good outcome. Recent arterial spin labeling (ASL) studies suggest that patients with hyperperfusion after treatment have a better clinical recovery. This study aimed to determine whether there was a distinctive magnetic resonance spectroscopy (MRS) metabolite profile in hyperperfused tissue after stroke reperfusion therapy. We studied 77 ischemic stroke patients 24 hours after treatment using MRS (single voxel spectroscopy, point resolved spectroscopy, echo time 30 ms), ASL, and diffusion-weighted imaging (DWI). Magnetic resonance spectroscopy voxels were placed in cortical tissue that was penumbral on baseline perfusion imaging but had reperfused at 24 hours (and did not progress to infarction). Additionally, 20 healthy age matched controls underwent MRS. In all, 24 patients had hyperperfusion; 36 had reperfused penumbra without hyperperfusion, and 17 were excluded due to no reperfusion. Hyperperfusion was significantly related to better 3-month clinical outcome compared with patients without hyperperfusion ( P = 0.007). Patients with hyperperfusion showed increased glutamate ( P

Background and Purpose— Magnetic resonance perfusion (MRP) and computed tomographic perfusion (CTP) are being increasingly applied in acute stroke trials and clinical practice, yet the comparability of their perfusion values is not well validated. The aim of this study was to validate the comparability of CTP and MRP measures. Methods— A 3-step approach was used. Step 1 was a derivation step, where we analyzed 45 patients with acute ischemic stroke who had both CTP and MRP performed within 2 hours of each other and within 9 hours of stroke onset. In this step, we derived the optimal perfusion map with the least difference between MRP and CTP. In step 2, the optimal map was validated on whole-brain perfusion data of 15 patients. Step 3 was to apply the optimal perfusion map to define cross-modality reperfusion from acute CTP to 24-hour MRP in 45 patients and, in turn, to assess how accurately this predicted 3-month clinical outcome. Results— Among 8 different perfusion maps included in this study, time to peak of the residual function ( T max ) was the only one with a nonsignificant difference between CTP and MRP in delineating perfusion defects. This was validated on whole-brain perfusion data, showing high concordance of T max between the 2 modalities (concordance correlation coefficient of Lin, >0.91); the best concordance was at 6 s. At T max >6 s threshold, MRP and CTP reached substantial agreement in mismatch classification (κ >0.61). Cross-modality reperfusion calculated by T max >6 s strongly predicted good functional outcome at 3 months (area under the curve, 0.979; P Conclusions— MRP and CTP can be used interchangeably if one uses T max measurement.

Objective: The purpose of this study was to examine susceptibility factors in thalamic stroke, as well as outcomes in order to identify rehabilitation needs.Methods: Ten patients with thalamic stroke were interviewed and administered the Audio Recorded Cognitive Screen. Magnetic resonance imaging (MRI) scans were examined to determine location and size of the lesion, as well as basilar artery size and anatomical variances in the circle of Willis.Results: Risk factors such as high cholesterol, high blood pressure and pre-existing heart conditions were identified. Circle of Willis variations were found in 6 of the 10 participants, with MR angiography indicating that the posterior communication artery was absent or failed to join the posterior cerebral artery. Basilar artery diameter measurements were no larger than normal. All participants reported post-stroke changes, including decreased coordination and mobility, poor balance, reduced energy, memory deficits and mood changes. Participants’ overall scores on cognitive tests were significantly lower than age-matched norms. Performance on the test domains of memory, fluency, language and attention were all significantly below age norms.Conclusions: The variability of outcome measures demonstrates the difficulty of defining patterns of relationship between risk factors and severity of functional sequelae in thalamic stroke.

Background The most effective and efficient model for providing organized stroke care remains uncertain. This study aimed to compare the effect of two models in a randomized controlled trial. Methods Patients with acute stroke were randomized on day one of admission to combined, co-located acute/rehabilitation stroke care or traditionally separated acute/rehabilitation stroke care. Outcomes measured at baseline and 90 days post-discharge included functional independence measure, length of hospital stay, and functional independence measure efficiency (change in functional independence measure score ÷ total length of hospital stay). Results Among 41 patients randomized, 20 were allocated co-located acute/rehabilitation stroke care and 21 traditionally separated acute/rehabilitation stroke care. Baseline measurements showed no significant difference. There was no significant difference in functional independence measure scores between the two groups at discharge and again at 90 days postdischarge (co-located acute/rehabilitation stroke care: 103·6 ± 22·2 vs. traditionally separated acute/rehabilitation stroke care: 99·5 ± 27·7; P = 0·77 at discharge; co-located acute/rehabilitation stroke care: 109·5 ± 21·7 vs. traditionally separated acute/rehabilitation stroke care: 104·4 ± 27·9; P= 0·8875 at 90 days post-discharge). Total length of hospital stay was 5·28 days less in co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (24·15 ± 3·18 vs. 29·42 ± 4·5, P = 0·35). There was significant improvement in functional independence measure efficiency score among participants assigned to co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (co-located acute/rehabilitation stroke care: median 1·60, interquartile range: 0·87–2·81; traditionally separated acute/rehabilitation stroke care: median 0·82, interquartile range: 0·27–1·57, P = 0·0393). Linear regression analysis revealed a high inverse correlation ( R2 = 0·89) between functional independence measure efficiency and time spent in the acute stroke unit. Conclusion This proof-of-concept study has shown that co-located acute/rehabilitation stroke care was just as effective as traditionally separated acute/rehabilitation stroke care as reflected in functional independence measure scores, but significantly more efficient as shown in greater functional independence measure efficiency. Co-located acute/rehabilitation stroke care has potential for significantly improved hospital bed utilization with no patient disadvantage.

Background and Purpose— Arterial spin labeling (ASL) is a perfusion magnetic resonance imaging (MRI) technique that does not require contrast administration and thus may be more practical in hyperacute stroke than susceptibility-weighted bolus-tracking perfusion-weighted imaging (PWI). However, a threshold for ASL measurement of the ischemic penumbra needs to be determined. Methods— A total of 58 patients with acute hemispheric ischemic stroke were imaged within 6 hours of symptom onset with MRI including ASL, diffusion-weighted MRI (DWI), and PWI, after perfusion computed tomography (CTP). Patients had repeat MRI at 24 hours. On repeat imaging, 32 patients did not reperfuse and were used to determine the penumbra threshold. A receiver-operating curve and a volumetric analysis were undertaken to identify the ASL-cerebral blood flow (CBF) threshold for the acute penumbra compared with the 24-hour DWI lesion in patients without reperfusion and with the acute PWI and CTP-Tmax thresholds. Results— An ASL-CBF threshold of 40% showed the highest area under the curve (AUC) for detection of the acute penumbra, defined by 24-hour DWI in nonreperfused patients (AUC 0.76, 95% confidence interval, 0.63–0.85), and was also accurate compared with the acute PWI-Tmax+6 seconds penumbral threshold (AUC 0.79, 95% confidence interval, 73–84) and acute CTP-Tmax 5.5 seconds penumbral threshold (AUC 0.77, 95% confidence interval, 72–84). Using a perfusion-to-diffusion mismatch ratio of 1.8:1, an ASL-CBF 40% mismatch compared with PWI-Tmax+ 6 seconds-DWI and CTP mismatch showed good sensitivity (0.81) and specificity (0.71). Conclusions— ASL-DWI mismatch shows potential to identify salvageable tissue in hyperacute stroke.

Delay in cortical vein filling during the late-venous phase (delayed-LCVF) is characterized by opacification of cerebral veins despite contrast clearance from contralateral veins on dynamic computed tomography angiography (dCTA) in acute ischemic stroke (AIS) patients. The aim of the study was to investigate the associations of delayed-LCVF with clot location, reperfusion status at 24 hours, and 90-days functional outcome in AIS patients who received reperfusion therapy. A prospective cohort of AIS patients treated with intravenous thrombolysis was studied. Groupwise comparison, univariate, and multivariate regression analyses were used to study the association of delayed-LCVF with clot location and clinical outcomes. Of 93 patients (mean age = 72 ± 12 years) with hemispheric AIS included in the study, 46 (49%) demonstrated delayed-LCVF. Patients with delayed-LCVF demonstrated a significantly higher proportion of proximal occlusion (72% vs 13%, P =

Objective:To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with tenecteplase compared to alteplase.Methods:Pooled clinical and imaging data from 2 phase 2 randomized trials comparing tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs).Results:From 146 pooled patients, 69 had a TICI 0/1 occlusion overall at baseline. Tenecteplase-treated patients with a complete vessel occlusion had greater complete recanalization rates at 24 hours (71% for tenecteplase vs 43% for alteplase, p < 0.001). Patients with a TICI 0/1 occlusion who were treated with tenecteplase also showed greater early clinical improvement (median NIHSS change with tenecteplase was 9, interquartile range [IQR] 6, alteplase 1, IQR 1, p = 0.001) and higher rates of favorable 90-day outcomes (mRS 0–1 of tenecteplase compared with alteplase, OR 4.82, 95% confidence interval 1.02–7.84, p = 0.05).Conclusions:Tenecteplase may offer greater recanalization efficacy compared to alteplase, possibly exaggerated in patients with complete vessel occlusions on baseline CTA.

Background and Purpose— Implementation of nurse-initiated protocols to manage fever, hyperglycemia, and swallowing dysfunction decreased death and disability 90 days poststroke in the QASC trial (Quality in Acute Stroke Care) conducted in 19 Australian acute stroke units (2005–2010). We now examine long-term all-cause mortality. Methods— Mortality was ascertained using Australia’s National Death Index. Cox proportional hazards regression compared time to death adjusting for correlation within stroke units using the cluster sandwich (Huber–White estimator) method. Primary analyses included treatment group only unadjusted for covariates. Secondary analysis adjusted for age, sex, marital status, education, and stroke severity using multiple imputation for missing covariates. Results— One thousand and seventy-six participants (intervention n=600; control n=476) were followed for a median of 4.1 years (minimum 0.3 to maximum 70 months), of whom 264 (24.5%) had died. Baseline demographic and clinical characteristics were generally well balanced by group. The QASC intervention group had improved long-term survival (>20%), but this was only statistically significant in adjusted analyses (unadjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.58–1.07; P =0.13; adjusted HR, 0.77; 95% CI, 0.59–0.99; P =0.045). Older age (75–84 years; HR, 4.9; 95% CI, 2.8–8.7; P P P =0.042) was associated with increased likelihood of survival. Cardiovascular disease (including stroke) was listed either as the primary or secondary cause of death in 80% (211/264) of all deaths. Conclusions— Our results demonstrate the potential long-term and sustained benefit of nurse-initiated multidisciplinary protocols for management of fever, hyperglycemia, and swallowing dysfunction. These protocols should be a routine part of acute stroke care. Clinical Trial Registration— URL: http://www.anzctr.org.au . Unique identifier: ACTRN12608000563369.

Background: Intravenous thrombolysis is one of few evidence-based treatments for acute stroke. Treatment uptake is low outside major stroke care centres. There is a need for greater understanding of barriers encountered by clinicians when seeking to increase thrombolysis rates. Aim: The aim of this study is to describe physicians’ and nurses’ perceptions regarding thrombolysis for acute stroke at hospitals in the earlier stages of thrombolysis implementation. Methods: A cross-sectional paper survey completed by physicians’ and nurses’ was distributed to 1127 staff at stroke care units, emergency departments or equivalent stroke care facilities at 19 Australian hospitals, as part of a cluster randomised controlled trial for thrombolysis implementation and systems improvement. Results: Of 1127 potential participants, 503 (148 physicians and 355 nurses) completed surveys (45% response rate). Over 90% agreed that thrombolysis improved the odds of independent survival. However, 42% to 58% agreed that there were limitations in the evidence base. A small proportion of staff indicated deficits in technical competencies. Interactive or competency-based training was reported by less than two-thirds of the sample. Challenges such as quick bed availability were identified. Emergency department physicians were less positive towards the treatment compared with nurses (p Conclusion: Australian hospitals seeking to address barriers to stroke thrombolysis implementation may benefit from the availability of interactive and competency-based training, staff performance feedback, support to make beds available quickly and bypass arrangements to quickly deliver acute stroke patients to appropriate facilities.

Background and Hypothesis Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4.5 h of ischemic stroke onset. However, tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients. We hypothesized that anterior circulation ischemic stroke patients, selected with ‘dual target’ vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging ‘mismatch’ within 4.5 h of onset, would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone. Study Design EXTEND-IA is an investigator-initiated, phase II, multicenter prospective, randomized, open-label, blinded-endpoint study. Ischemic stroke patients receiving standard 0.9 mg/kg intravenous tissue plasminogen activator within 4.5 h of stroke onset who have good prestroke functional status (modified Rankin Scale 1.2, absolute mismatch >10 ml, ischemic core volume Study Outcomes The coprimary outcome measure will be reperfusion at 24 h and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Secondary outcomes include modified Rankin Scale at day 90, death, and symptomatic intracranial hemorrhage.

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

Objective This paper identified barriers which prevent rural health care providers from utilising rt-PA in acute ischaemic stroke and proposes possible support mechanisms to increase its utilisation. Methods This descriptive study uses data from anonymous surveys distributed to health care providers involved in acute stroke patient care in three rural hospitals with rt-PA pathways. Saturation sampling was used. Surveys gathered self assessed ratings of experience, practice environment, attitudes, existing support, barriers and possible enablers regarding rt-PA use in acute stroke. Results Physicians reported the strongest barriers to the use of rt-PA in acute stroke as pre-hospital delays (91%), risk of intracerebral haemorrhage (ICH) (73%) and clinical diagnostic uncertainty (60%). They reported high levels of confidence in the support received from their stroke units (90%). Nurses identified a poor level of stroke education and knowledge on rt-PA utilisation in acute stroke. A third of nurses could correctly list six different stroke signs. The risk of ICH following rt-PA administration in stroke was also a significant barrier for nurses. Response rate from physicians was 26% (10/38) and 19% (13/69) for nurses. Conclusions To reduce barriers to rt-PA utilisation in rural facilities physicians require education on the calculated risk of ICH as well as exposure and experience to improve their ability to confidently diagnose stroke patients who are eligible for rt-PA treatment. Education for nurses on symptoms of stroke and rt-PA utilisation and administration is recommended.

A shift is emerging in the way in which we view post-stroke recovery. This shift, supported by evidence from neuroimaging studies, encourages us to look beyond the lesion and to identify viable brain networks with capacity for plasticity. In this article, the authors review current advances in neuroimaging techniques and the new insights that they have contributed. The ability to quantify salvageable tissue, evidence of changes in remote networks, changes of functional and structural connectivity, and alterations in cortical thickness are reviewed in the context of their impact on post-stroke recovery. The value of monitoring spared structural connections and functional connectivity of brain networks within and across hemispheres is highlighted.

Rationale No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. Aim The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation ‘spot sign’ will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4·5-hours of stroke onset compared with placebo. Design The Spot sign and Tranexamic acid On Preventing ICH growth – AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume Study outcomes The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. Discussion This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636.

Objective This audit of activity reports on current rates of recombinant tissue plasminogen activator (rt-PA) use within specialised stroke care units in rural New South Wales (NSW). It measures stroke onset-to-treatment time and morbidity outcomes for patients treated with rt-PA and aims to establish the safety and effectiveness of rt-PA use in rural NSW. Design, setting and participants Medical records reviews of patients admitted with acute ischaemic stroke at two rural NSW hospitals between 1 July 2008 and 30 June 2010. Main outcome measures Treatment with rt-PA, morbidity scores 5 days post-stroke or discharge, incidence of intracranial haemorrhage and mortality rate 6 months post-stroke were recorded. Treatment protocol violations were assessed and time to treatment from stroke onset and hospital admission. Results Of 605 patients admitted with acute ischaemic stroke, 20 (3.3%) received rt-PA treatment. Of these two, 10% had symptomatic intracranial haemorrhage and one died within 6 months. Morbidity scores for those treated with rt-PA were similar to those not treated. The median onset-to-needle time was 2 hours and 34 min, and the median door-to-needle time was 1 hour and 40 min. There were no treatment protocol violations. Conclusion Recombinant tissue plasminogen activator can be delivered in rural Australian hospitals in a timely manner within recommended implementation guidelines. Acute stroke thrombolytic services in rural Australian facilities had comparable outcomes to metropolitan facilities. Small numbers of thrombolysed patients prevented a validation study of the well-defined outcome benefits from rt-PA. The need for ongoing data collection in regional settings is supported.

Background. Cardiorespiratory fitness is low after stroke. Improving fitness has the potential to improve function and reduce secondary cardiovascular events. Objective. This review with meta-analysis aims to identify characteristics and determine the effectiveness of interventions to improve cardiorespiratory fitness after stroke. Methods. A systematic search and review with meta-analysis was undertaken. Key inclusion criteria were the following: peer-reviewed articles published in English, adult stroke survivors, an intervention with the potential to improve cardiorespiratory fitness, and peak oxygen consumption (VO2peak) assessed preintervention and postintervention via a progressive aerobic exercise test. Results. From 3209 citations identified, 28 studies were included, reporting results for 920 participants. Studies typically included chronic, ambulant participants with mild to moderate deficits; used an aerobic or mixed (with an aerobic component) intervention; and prescribed 3 sessions per week for 30 to 60 minutes per session at a given intensity. Baseline VO2peak values were low (8-23 mL/kg/min). Meta-analysis of the 12 randomized controlled trials demonstrated overall improvements in VO2peak of 2.27 (95% confidence interval = 1.58, 2.95) mL/kg/min postintervention. A similar 10% to 15% improvement occurred with both aerobic and mixed interventions and in shorter (≤3 months) and longer (>3 months) length programs. Only 1 study calculated total dose received and only 1 included long-term follow-up. Conclusions. The results demonstrate that interventions with an aerobic component can improve cardiorespiratory fitness poststroke. Further investigation is required to determine effectiveness in those with greater impairment and comorbidities, optimal timing and dose of intervention, whether improvements can be maintained in the longer term, and whether improved fitness results in better function and reduced risk of subsequent cardiovascular events.

Objective Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. Methods The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p 8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. Interpretation VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;73:510–519

Whole-brain dynamic time-resolved computed tomography angiography (CTA) is a technique developed on the new 320-detector row CT scanner capable of generating time-resolved cerebral angiograms from skull base to vertex. Unlike a conventional cerebral angiogram, this technique visualizes pial arterial filling in all vascular territories, thereby providing additional hemodynamic information. Ours was a retrospective study of consecutive patients with ischemic stroke and M1 middle cerebral artery +/– intracranial internal carotid artery occlusions presenting to our center from June 2010 and undergoing dynamic time-resolved CTA and perfusion CT within 6 hours of symptom onset. Leptomeningeal collateral status was assessed by determining relative prominence of pial arteries in the ischemic region, rate and extent of retrograde flow, and various topographical patterns of pial arterial filling. Twenty-five patients were included in the study. We demonstrate the existence of the following novel properties of leptomeningeal collaterals in humans: (a) posterior (posterior cerebral artery (PCA)–MCA) dominant collateralization, (b) intra-territorial ‘within MCA region’ leptomeningeal collaterals, and (c) significant variability in size, extent, and retrograde filling time in pial arteries. We also describe a simple and reliable collateral grading template that, for the first time on dynamic CTA, incorporates back-filling time as well as size and extent of collateral filling.

Sports-related concussion (SRC) is typically associated with functional, as opposed to structural, injury. The results of traditional structural neuroimaging techniques used to assess SRC tend to be normal in many athletes, and are only clinically helpful in ruling out a more serious injury. Diffusion tensor imaging (DTI) has increasingly been touted as a method offering greater clinical potential in mild traumatic brain injury (mTBI). Despite this, the utility of DTI as a clinical tool for diagnosing and managing SRC has received considerably less attention than it has in the general TBI research literature. The aim of this article is to conduct a systematic review of DTI in SRC, and to provide a focus and overview of research findings using this MRI technique in SRC. A systematic review of articles published in the English language, up to February 2012, was retrieved via PsycINFO(®), MEDLINE(®), EMBASE, SPORTDiscus(™), Scopus, Web of Science, and Informit; using the key search terms: diffusion tensor imaging, diffusion magnetic resonance imaging, diffusion weighted MRI, diffusion MRI, fractional anisotropy, tractography, apparent diffusion coefficient, magnetic resonance imaging, mild traumatic brain injury, mTBI, traumatic brain injury, concussion, sport, athletic and athlete. Observational, cohort, correlation, cross-sectional and longitudinal studies were all included in the current review. Results of the review found eight articles that met inclusion criteria, which included data on 214 athletes and 96 controls. Seven of eight studies reported some type of DTI abnormality, although the neuroanatomical sites involved varied. Although considerable methodological variations exist across studies, the current review suggests that DTI may possess adequate diagnostic sensitivity to detect SRC in affected athletes. Further longitudinal studies are required to demonstrate its discriminate validity and prognostic capacity within this field.

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.

Background and Purpose— Uncertainty exists over whether quality improvement strategies translate into better health-related quality of life (HRQoL) and survival after acute stroke. We aimed to determine the association of best practice recommended interventions and outcomes after stroke. Methods— Data are from the Australian Stroke Clinical Registry during 2010 to 2014. Multivariable regression was used to determine associations between 3 interventions: received acute stroke unit (ASU) care and in various combinations with prescribed antihypertensive medication at discharge, provision of a discharge care plan, and outcomes of survival and HRQoL (EuroQoL 5-dimensional questionnaire visual analogue scale) at 180 days, by stroke type. An assessment was also made of outcomes related to the number of processes patients received. Results— There were 17 585 stroke admissions (median age 77 years, 47% female; 81% managed in ASUs; 80% ischemic stroke) from 42 hospitals (77% metropolitan) assessed. Cumulative benefits on outcomes related to the number of care processes received by patients. ASU care was associated with a reduced likelihood of death (hazard ratio, 0.49; 95% confidence interval, 0.43–0.56) and better HRQoL (coefficient, 21.34; 95% confidence interval, 15.50–27.18) within 180 days. For those discharged from hospital, receiving ASU+antihypertensive medication provided greater 180-day survival (hazard ratio, 0.45; 95% confidence interval, 0.38–0.52) compared with ASU care alone (hazard ratio, 0.64; 95% confidence interval, 0.54–0.76). HRQoL gains were greatest for patients with intracerebral hemorrhage who received care bundles involving discharge processes (range of increase, 11%–19%). Conclusions— Patients with stroke who receive best practice recommended hospital care have improved long-term survival and HRQoL.

A new concussion interchange rule (CIR) was introduced in 2014 for the National Rugby League and National Youth Competition (NYC). The CIR allows a player suspected of having sustained a concussion to be removed from play and assessed without an interchange being tallied against the player’s team. Participants included all NYC players who used the CIR during the 2014 season. 2 raters completed video analysis of 131 (of a total of 156 reported) uses of the CIR, describing injury characteristics, situational factors, and concussion signs. The incidence rate was 44.9 (95% CI: 38.5–52.3) uses of the CIR per 1 000 NYC player match hours, or approximately one CIR use every 1.3 games. Apparent loss of consciousness/unresponsiveness was observed in 13% of cases, clutching the head in 65%, unsteadiness of gait in 60%, and a vacant stare in 23%. Most incidences occurred from a hit-up (82%). There appeared to be some instances of video evidence of injury but the athlete was cleared to return to play in the same game. Video review appears to be a useful adjunct for identifying players suffering possible concussion. Further research is required on the usefulness of video review for identifying signs of concussive injury.

Cervical artery dissection (CAD) is a leading cause of stroke among middle-aged adults, but the etiology is unclear. Some reports of seasonal variation in CAD incidence have been suggested but may reflect extreme climatic conditions. Seasonal variation may implicate more transient seasonal causes such as proinflammatory or hypercoagulable states. This study aimed to assess whether CAD incidence varied with season between UK and Australian sites. Also, this study aimed to determine whether there was a different pattern of seasonal variation between arteries (carotid and vertebral) and any association between CAD incidence and clinical factors.This was a retrospective observational study of patients older than 18 years with radiological diagnosis of internal carotid or vertebral arterial dissection, from sites in Australia and the UK. Clinical variables were compared between autumn-winter and spring-summer and site of dissection.A total of 133 CAD cases were documented in Australia and 242 in the UK. There was a seasonal pattern to CAD incidence in countries in both the northern and the southern hemispheres, with a trend for dissection to occur more commonly in autumn, winter, and spring than in summer (incidence rate ratios [IRR] 1.4-1.5, P .05). CAD counts were also slightly higher in internal carotid than in vertebral artery (IRRs 1.168, 1.43, and 1.127, respectively). Neither systolic blood pressure nor pulse pressure was significantly associated with CAD counts.CAD occurs more commonly in cooler months regardless of geographical location, suggesting transient seasonal causes may be important in the pathophysiology. This effect was slightly higher in internal carotid than in vertebral artery, suggesting differing trigger mechanisms between dissection sites.

Objectives: To investigate differences in management and outcomes for patients admitted to the hospital with TIA according to care on a stroke unit (SU) or alternate ward setting up to 180 days post event. Methods: TIA admissions from 40 hospitals participating in the Australian Stroke Clinical Registry during 2010–2013 were assessed. Propensity score matching was used to assess outcomes by treatment group including Cox proportional hazards regression to compare survival differences and other appropriate multivariable regression models for outcomes including health-related quality of life and readmissions. Results: Among 3,007 patients with TIA (mean age 73 years, 54% male), 1,110 pairs could be matched. Compared to management elsewhere in hospitals, management in an SU was associated with improved cumulative survival at 180 days post event (hazard ratio 0.57, 95% confidence interval 0.35–0.94; p = 0.029), despite not being statistically significant at 90 days (hazard ratio 0.66, 95% confidence interval 0.33–1.31; p = 0.237). Overall, there were no differences for being discharged on antihypertensive medication or with a care plan, and the 90- to 180-day self-reported outcomes between these groups were similar. In subgroup analyses of 461 matched pairs treated in hospitals in one Australian state (Queensland), patients treated in an SU were more often prescribed aspirin within 48 hours (73% vs 62%, p < 0.001) and discharged on antithrombotic medications (84% vs 71%, p < 0.001) than those not treated in an SU. Conclusions: Hospitalized patients with TIA managed in SUs had better survival at 180 days than those treated in alternate wards, potentially through better management, but further research is needed.

Background Cervical artery dissection (CAD) is a leading cause of ischemic stroke among middle aged adults, yet the aetiology remains poorly understood. There are reports from colder northern hemisphere sites of a seasonal pattern in the incidence of CAD. Seasonality may suggest some transient putative pro-inflammatory mechanism but it is unknown whether this also exists in temperate climates. Aims To investigate the seasonal variation in incidence of CAD in the xx Region, Australia, and to compare seasonal incidence and selected clinical features between cases of carotid and vertebral artery dissection. Methods This retrospective observational study investigated seasonal variation in CAD from a regional stroke register between 2006 and 2014. Clinical features and site of dissection were dichotomized into autumn-winter and spring-summer groups and compared with Chi 2 analysis. Results 61 CAD events were identified. A strong trend was identified for CAD to occur more frequently in autumn-winter compared to spring-summer (38, 62.30% vs. 23, 37.70%; p = 0.054). Males were significantly more likely to present with vertebral artery dissection (VAD) than females (27, 73.0% vs 10, 41.7%; p = 0.014). A history of mild trauma was more common in VAD than internal carotid artery dissection (ICAD) (14, 41.2% vs 3, 13.0%; p = 0.023). Cases of VAD were more likely to have had an elevated white cell count than ICAD (16, 47.1% vs 5, 20.8%; p = 0.041). Conclusions The findings suggest seasonal variation in the CAD incidence in a temperate region of Australia. Clinicians should be vigilant for CAD or risk of CAD during the colder months.

See Saver (doi:10.1093/awx020) for a scientific commentary on this article.Stroke shortens an individual's disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variables (e.g. ischaemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. We used data from a prospectively collected international, multicentre, observational registry of acute ischaemic stroke patients who had perfusion computed tomography and computed tomography angiography before treatment with intravenous alteplase. Baseline perfusion computed tomography and follow-up magnetic resonance imaging were analysed to derive the baseline penumbra volume, baseline ischaemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on Disability-Adjusted Life Year. Clinical variables were age, sex, National Institutes of Health Stroke Scale score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate disability-adjusted life-year due to stroke, such that 1 year of disability-adjusted life-year equates to 1 year of healthy life lost due to stroke. There were 772 patients receiving alteplase therapy. The number of disability-adjusted life-year days lost per 1 ml of baseline ischaemic core volume was 17.5 (95% confidence interval, 13.2-21.9 days, P < 0.001). For every millilitre of penumbra salvaged, 7.2 days of disability-adjusted life-year days were saved (β = -7.2, 95% confidence interval, -10.4 to -4.1 days, P < 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3-7.5 days, P = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not significantly associated with savings in disability-adjusted life-year days. Pretreatment perfusion computed tomography can (independently of clinical variables) predict significant gains, or loss, of disability-free life in patients undergoing reperfusion therapy for stroke. The effect of earlier treatment on disability-free life appears explained by salvage of penumbra, particularly when the ischaemic core is not too large.

Background: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. Methods: We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core Results: Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P =0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P =0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0–1: odds ratio, 1.77; 95% confidence interval, 0.89–3.51; P =0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P P =0.032) than those treated with alteplase. Conclusions: Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion–defined target mismatch. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01472926. URL: https://www.anzctr.org.au . Unique identifier: ACTRN12608000466347.

Background Stroke associated with acute carotid occlusion is associated with poor effectiveness of tissue plasminogen activator ( tPA ) thrombolysis and poor prognosis. Rupture of atherosclerotic plaques resulting in vascular occlusions may occur on plaques, causing variable stenosis. We hypothesized that degree of stenosis may affect recanalization rates with tPA . Ultrasound+ tPA (sonothrombolysis) has been shown to improve recanalization for intracranial occlusions but has not been tested for carotid occlusion. Our primary aim was to determine thrombolytic recanalization rates in a model of occlusion with variable stenosis, with a secondary aim to investigate sonothrombolysis in this model. Methods and Results Rat carotid arteries were crushed and focal stenosis created (25% baseline Doppler flow) with a silk‐suture tie invoking thrombosis and occlusion. To model mild or severe stenosis, the tie was released pretreatment or left in place. Animals were treated with tPA (10 mg/kg) or tPA +ultrasound (2‐MHz) in each stenosis model (n=7/group). Recanalization was assessed by Doppler flow. Thrombolytic recanalization rates were significantly higher in mild stenosis groups (71% versus 0% with severe stenosis; P Conclusions In this model, the degree of carotid stenosis had a large effect on thrombolytic recanalization. Sonothrombolysis using standard parameters for intracranial sonothrombolysis did not increase recanalization. Further testing is warranted. The degree of underlying stenosis may be an important predictor of thrombolytic recanalization, and clinical correlation of these findings may provide new approaches to treatment selection for patients with carotid occlusion.

The National Rugby League (NRL) in Australia introduced a new 'concussion interchange rule' (CIR) in 2014, whereby a player suspected of having sustained a concussion can be removed from play, and assessed, without an interchange being tallied against the player's team. We conducted a video analysis, describing player and injury characteristics, situational factors, concussion signs, and return to play for each "CIR" event for the 2014 season. There were 167 reported uses of the CIR. Apparent loss of consciousness/unresponsiveness was observed in 32% of cases, loss of muscle tone in 54%, clutching the head in 70%, unsteadiness of gait in 66%, and a vacant stare in 66%. More than half of the players who were removed under the CIR returned to play later in the same match (57%). Most incidences occurred from a hit up (62%) and occurred during a tackle where the initial contact was with the upper body (80%). The new concussion interchange rule has been used frequently during the first season of its implementation. In many cases, there appeared to be video evidence of injury but the athlete was cleared to return to play. More research is needed on the usefulness of video review for identifying signs of concussive injury.

Introduction: There remains uncertainty about the benefits of reperfusion therapy in minor stroke. In this study we tested the hypothesis that patients with a small perfusion lesions do not show clinical benefit from reperfusion therapy when using conventional outcome scores such as the modified Rankin scale. Methods: A prospective cohort of consecutive ischemic stroke patients who fulfilled standard clinical/NCCT eligibility criteria with additional perfusion and angiography CT before treatment with iv alteplase were collected. Volumetric CT perfusion was retrospectively analysed to identify patients with a small perfusion lesion (defined as a delay time lesion 3 seconds Results: Of the 1526 patients who were potentially eligible for alteplase therapy, 356 had a perfusion lesion Conclusion: Ischemic stroke patients with a small perfusion lesion appear to have an excellent natural history regardless of alteplase treatment. Patients with a visible vessel occlusion may have a slight benefit from treatment.

Background: EXTEND is an investigator-initiated, randomised, double-blind and placebo-controlled Phase III trial of intravenous alteplase vs placebo in patients with ischemic stroke 4.5-9 hours from stroke onset or wake-up-stroke (WUS). The prevalence of intra-cranial vessel occlusion in WUS patients remains to be determined and can guide the development of optimal therapy for this unique group of stroke patients. Objective: To study the prevalence and characteristics of intra-cranial vessel occlusion in this WUS cohort. Methods: Ischemic stroke patients within 4.5-9 hours from stroke onset or with WUS (time of WUS onset defined as the midpoint between time to sleep and awakening with the stroke symptoms) are eligible for enrollment. Criteria for entry into the trial include perfusion-diffusion mismatch using a perfusion threshold of Tmax>6sec and a perfusion:diffusion lesion volume ratio of >1.2. Diffusion lesion volume must be Results: 97 patients had images with adequate quality, including 63 (65%) in the WUS group with median age of 77.0 yrs (IQR 67.0, 81.0) and NIHSS of 14.0 (9.0, 19.0). 62 of 63 patients (98%) had vessel occlusion with 44.4% involving M1 of the middle cerebral artery, 17.5% M2, 4.8% M3, 25.4% both internal carotid artery (ICA) and M1, 4.8% ICA alone and 3.1% the posterior cerebral artery. The median ischemic core volume was 15.0 ml (6.5, 31.5), Tmax>6 volume 88.5ml (58.0, 122.0), mismatch volume 65.5ml (42.8, 92.0), and ratio of 4.8 (2.5, 8.7). 19 patients (30%) demonstrated recanalization on follow-up imaging. Conclusion: In WUS patients there is a very high rate of intracranial vessel occlusion with relatively large volumes of salvageable penumbral tissue. Intravenous thrombolytic therapy followed by thrombectomy in selected cases may be an appropriate therapeutic option with safety and efficacy remaining to be established in randomized controlled trials.

Background and Purpose— Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset Methods— The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P −6 and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. Results— One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P =9.5×10 −9 ). The associated locus is in an intergenic region between TCF7L2 and HABP2 . In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII–activating protease levels, a product of HABP2 . Conclusions— HABP2 , which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.

Background Fatigue is a common symptom in stroke survivors for which there is currently no proven therapy. Modafinil is a wakefulness-promoting agent with established benefits in other disease models. We aim to test if modafinil will improve patient’s self-reported fatigue scores when compared to placebo and if therapy results in increased quality of life. Methods/design MIDAS is a phase II, single-centre, prospective, double-blinded, randomised, crossover trial of modafinil for the treatment of persistent fatigue in survivors of ischaemic stroke. The inclusion criteria will require an average score of 12 or more across all domains of the Multi-dimensional Fatigue Inventory (MFI-20) and the diagnosis of a stroke more than 6 months prior. Patients will be randomised 1:1 to receive either modafinil 200 mg daily or placebo for a period of 6 weeks, after which a crossover will occur where patients who are on modafinil will begin taking placebo and vice versa. The primary outcome will be improvement in fatigue as measured by the MFI-20. Secondary outcomes will include changes in the Fatigue Severity Scale, improved cognition measured using the Montreal Cognitive Assessment, improvement in mood as determined by the Depression, Anxiety and Stress Scale and improvement in each patient’s stroke-specific quality of life score. All participants will also undergo magnetic resonance imaging (MRI) at baseline, crossover and study conclusion to measure cerebral blood flow on arterial spin labelling and brain activity on resting state functional MRI. This study will comply with the CONSORT guidelines. The projected sample size requirement is 36 participants in a crossover trial giving a power of 80 % and a type-1 error rate of 0.05. Discussion MIDAS seeks to enhance the quality of life in stroke survivors by assisting or resolving stroke-associated fatigue. Trial registration ACTRN12615000350527, registered on the 17 April 2015. Protocol version 3, approved 16 June 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1537-4) contains supplementary material, which is available to authorized users.

Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was underestimated when brain coverage was 40 mm or less (P < .0001). Conclusion Correct threshold setting and whole-brain coverage CT perfusion allowed differentiation of the penumbra from the ischemic core in patients with acute ischemic stroke. (©) RSNA, 2016 Online supplemental material is available for this article.

Internationally recognised evidence-based guidelines recommend appropriate triage of patients with stroke in emergency departments (EDs), administration of tissue plasminogen activator (tPA), and proactive management of fever, hyperglycaemia and swallowing before prompt transfer to a stroke unit to maximise outcomes. We aim to evaluate the effectiveness in EDs of a theory-informed, nurse-initiated, intervention to improve multidisciplinary triage, treatment and transfer (T3) of patients with acute stroke to improve 90-day death and dependency. Organisational and contextual factors associated with intervention uptake also will be evaluated. This prospective, multicentre, parallel group, cluster randomised trial with blinded outcome assessment will be conducted in EDs of hospitals with stroke units in three Australian states and one territory. EDs will be randomised 1:1 within strata defined by state and tPA volume to receive either the T3 intervention or no additional support (control EDs). Our T3 intervention comprises an evidence-based care bundle targeting: (1) triage: routine assignment of patients with suspected stroke to Australian Triage Scale category 1 or 2; (2) treatment: screening for tPA eligibility and administration of tPA where applicable; instigation of protocols for management of fever, hyperglycaemia and swallowing; and (3) transfer: prompt admission to the stroke unit. We will use implementation science behaviour change methods informed by the Theoretical Domains Framework [1, 2] consisting of (i) workshops to determine barriers and local solutions; (ii) mixed interactive and didactic education; (iii) local clinical opinion leaders; and (iv) reminders in the form of email, telephone and site visits. Our primary outcome measure is 90 days post-admission death or dependency (modified Rankin Scale >2). Secondary outcomes are health status (SF-36), functional dependency (Barthel Index), quality of life (EQ-5D); and quality of care outcomes, namely, monitoring and management practices for thrombolysis, fever, hyperglycaemia, swallowing and prompt transfer. Outcomes will be assessed at the patient level. A separate process evaluation will examine contextual factors to successful intervention uptake. At the time of publication, EDs have been randomised and the intervention is being implemented. This theoretically informed intervention is aimed at addressing important gaps in care to maximise 90-day health outcomes for patients with stroke. Australian and New Zealand Clinical Trials Registry ACTRN12614000939695 . Registered 2 September 2014.

SummaryIntroductionAssessment of cerebral hemodynamics with transcranial Doppler (TCD) can provide real-time, bed-side assessment of important prognostic variables in acute stroke such as the status of collateral flow and vessel recanalization status. In acute middle cerebral artery (MCA) occlusion, anterior cerebral artery (ACA) flow diversion (FD) is correlated with leptomeningeal collateral flow and may be a clinically useful prognostic indicator. Continuous TCD monitoring of MCA recanalization may also provide useful prognostic information including changes in flow pattern and the occurrence of microembolic signals (MES). We present studies examining associations between ACA FD, MCA recanalization and MES patterns on the characteristics of ischemia and infarction in acute MCA stroke.MethodsPatients studied were consecutive sub-6h from onset internal carotid artery (ICA) territory ischemic stroke cases. A subset of these cases with MCA occlusion were studied with 2h of continuous MCA monitoring. All patients underwent baseline multimodal computed tomographic (CT) scanning, baseline diagnostic TCD, and 24h post stroke magnetic resonance (MR) imaging. All MCA occlusion patients studied with continuous monitoring were treated with intravenous thrombolysis. ACA flow diversion was defined as ipsilateral mean velocity of 30% or greater than the contralateral artery. Recanalization status was assessed using the Thrombolysis In Brain ischemic (TIBI) grading system and MES counted “off-line” by experienced observers. Leptomeningeal collateralisation (LMC) was graded on CT angiography. Infarct core and penumbral volumes were defined using CT perfusion thresholds. Infarct volume, reperfusion, and vessel status were measured at 24h using MR techniques. In patients undergoing recanalization monitoring, comparison was made between those with and without major reperfusion. Multivariable regression analysis was performed to assess for any associations between ACA flow diversion, TIBI grades and MES on infarction controlling for other important clinical variables.ResultsFlow diversion: 53 patients qualified for FD analysis. ACA FD was associated with good collateral flow on CT angiography (p

The mismatch between a larger perfusion lesion and smaller diffusion lesion on magnetic resonance imaging is a validated signal of the ischemic penumbra, namely the region at risk in acute ischemic stroke that is critically hypoperfused and the target of reperfusion therapies. Clinical trials have shown strong correlations between reperfusion in mismatch patients and improved clinical outcomes. Attenuation of infarct growth is associated with reperfusion and corresponding clinical gains. Using computed tomography perfusion, the mismatch between relative cerebral blood flow or cerebral blood volume and perfusion delay is a comparable penumbral marker. Automated techniques allow rapid quantitative assessment of mismatch with thresholding to exclude benign oligemia. The penumbra is often present beyond the current 4.5-h time window, defined for the use of intravenous tPA. Treatment beyond this time point remains investigational. Although the efficacy of thrombolysis in mismatch patients requires further validation in randomized trials, there is now sufficient evidence to recommend that advanced neuroimaging of mismatch should be used for selection of delayed therapies in phase 3 trials.

Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent.In this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale on which higher scores indicate more severe neurologic deficits).The three treatment groups each comprised 25 patients. The mean (±SD) NIHSS score at baseline for all patients was 14.4±2.6, and the time to treatment was 2.9±0.8 hours. Together, the two tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P0.001) at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; P=0.02).Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. (Funded by the Australian National Health and Medical Research Council; Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347.).

Background Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke. Methods Published original English-language research from four electronic databases spanning 1997–2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted. Results Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio = 2.1, p = 0.05). Conclusions In order to improve IV tPA rates in acute stroke care, specific health system factors need to be targeted. Multi-component quality improvement approaches can improve IV tPA rates for stroke, although more thoughtfully designed and well-reported trials are required to safely increase rates of IV tPA to eligible stroke patients.

We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery. One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5 h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24 h after stroke onset, including single-voxel, short-echo-time (30 ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area. The concentrations of total creatine (5.39 vs 5.85 mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13 mM ± 1.57, p

Tissue plasminogen activator (tPA) is the only approved thrombolytic therapy for acute ischemic stroke, yet many patients do not recanalize. Enhancing thrombolytic efficacy of tPA is a major focus of stroke research. Traditionally, a “rat dose” of 10 mg/kg has been used in rodent models. Recent studies suggested that the clinical “human” dose (0.9 mg/kg) may better mimic clinical recanalization. These studies only compared the rat and clinical doses and so we aimed to test recanalization efficacy of multiple tPA doses ranging from 0.9 to 10 mg/kg in a model of endothelial injury and vessel stenosis. The common carotid artery of rats was crushed and stenosed to allow in-situ occlusive thrombus formation (Folt’s model of ‘physiological’ thrombus). Intravenous tPA was administered 60 minutes post-occlusion (n = 6-7/group). Sustained recanalization rates were 0%, 17%, 67% and 71%, for 0.9, 1.8, 4.5 and 10 mg/kg, respectively. Median time to sustained recanalization onset decreased with increasing dosage. We conclude that 10 mg/kg of tPA is too effective, whereas 0.9 mg/kg is ineffective for lysis of occlusive thrombi formed in situ. Neither dose mimics clinical tPA responses. A dose of 2x the clinical dose is a more appropriate mimic of clinical tPA recanalization in this model.

Background and Purpose— CT perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke but has limited validation. Cerebral blood volume (CBV) has been proposed as the best predictor of infarct core. We tested CBV against other common CTP parameters using contemporaneous diffusion MRI. Methods— Patients with acute ischemic stroke Results— In analysis of 98 CTP slabs (54 patients, median onset to CT 190 minutes, median CT to MR 30 minutes), relative CBF performed best (AUC, 0.79; 95% CI, 0.77–81), significantly better than absolute CBV (AUC, 0.74; 95% CI, 0.73–0.76). The optimal threshold was Conclusions— In contrast to previous reports, CBF corresponded with the acute diffusion-weighted imaging lesion better than CBV, although no single threshold avoids detection of false-positive regions in unaffected white matter. This relates to low signal-to-noise ratio in CTP maps and emphasizes the need for optimized acquisition and postprocessing.