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The aim of this study was to explore the perspectives of people with stroke and their whānau on barriers to accessing best practice care across Aotearoa, and to brainstorm potential solutions.We conducted ten focus groups nationwide and completed a thematic analysis.Analysis of the data collected from the focus groups identified five themes: (1) inconsistencies in stroke care; (2) importance of effective communication; (3) the role of whānau support; (4) the need for more person rather than stroke centred processes; and (5) experienced inequities. Participants also identified potential solutions.Key recommendations include the need for improved access to stroke unit care for rural residents, improved post-discharge support and care coordination involving the whānau, improved communication across the patient journey, and a concerted effort to improve culturally safe care. Next step is to implement and monitor these recommendations.

Background and Purpose: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. Methods: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0–2) at day 90. Results: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4–5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1–5.7]) alteplase patients ( P =0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7–6.2] versus 1 [0.4%; 95% CI, 0.01–2.2], P =0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P =0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14–2.80], P =0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74–1.95], P =0.46). Conclusions: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.

Sudden catastrophic events such as terror attacks have clear and immediate consequences for the people who are directly affected. However, less is known about the impact on the physical health of local community members (online supplemental available from Dryad [doi.org/10.5061/dryad.bcc2fqz9t][1] for further discussion). Acute psychological stress may cause a parallel physiologic response increasing risk of cardiovascular events.1–3 On March 15, 2019, a gunman shot and killed 51 people praying at the Al Noor and Linwood mosques in Christchurch city, New Zealand. We observed an increase in ischemic stroke reperfusion treatments in the week starting Monday, March 18, 3 days after the terror attack. We hypothesized that this observation could have occurred because of either an effect of the attack on the total number of ischemic strokes and/or the severity of these strokes, or coincidence. We investigated these possibilities by analyzing the association between the terror attack and rate of stroke reperfusion treatment, proven intracranial large vessel occlusion (LVO), and total stroke admissions at Christchurch hospital and the national stroke data set. [1]: https://doi.org/10.5061/dryad.bcc2fqz9t

Purpose To describe interventionalist and workflow characteristics of an acute stroke endovascular thrombectomy (EVT) center without a dedicated interventional neuroradiology service and report clinical and radiologic outcomes. Materials and Methods Retrospective review was performed of all patients receiving EVT at Christchurch Hospital, New Zealand, from June 2014 to the end of December 2019 from a prospective reperfusion registry. During the study period, 5 peripheral vascular interventional radiologists, 2 of whom had experience in other neuroendovascular procedures, performed 210 EVT procedures. Median age of patients was 76 years (interquartile range: 64–83 y), and 107 (51%) were men. Results The most commonly occluded vessel was the M1 middle cerebral artery (n = 114; 54%). Successful reperfusion (Modified Treatment In Cerebral Ischemia score 2b–3) was achieved in 180 (86%) procedures. Favorable 90-day outcome (modified Rankin Scale score 0–2) was achieved in 102 (54%) patients with no disability before stroke. Symptomatic intracranial hemorrhage occurred in 3 (1.4%) patients. Treatment rates in the local catchment area increased from 6 per 100,000 population in 2017 to 15 per 100,000 in 2019. Conclusions The results of this study suggest peripheral vascular interventional radiologists with specific training can successfully perform EVT resulting in a significant increase in EVT provision.

Introduction: Stroke care provision differs between urban and provincial hospitals predominantly due to economy of scale, which is correlated with resources available and degree of specialisation. We assessed the impact of urban versus non-urban hospital location on stroke outcomes. Methods: REGIONS Care is a New Zealand (NZ) nationwide prospective observational study that included consecutively admitted stroke patients involving all NZ stroke hospitals between 1 May and 31 October 2018. Patients were followed-up at 3, 6, and 12 months. The primary outcome was favourable modified Rankin Score of 0-2. Results were adjusted for age, stroke severity, pre-morbid level of independence and other potential confounders using multivariate logistic regression. Results: Of the 2,379 patients (mean age (SD), 75 (13.7)), 1,963 (82.6%) had ischaemic strokes and 291 (12.3%) haemorrhagic strokes. The odds of achieving a favourable outcome at 3 and 6 months was significantly lower for patients treated in non-urban compared to urban hospitals: aOR 0.72 (95%CI:0.56-0.93; p=0.012) and aOR 0.71 (95%CI:0.52-0.96; p=0.028), respectively. At 12-months this difference was less pronounced (aOR 0.77, 95%CI:0.57-1.04; p=0.089). Similarly, death was significantly more likely at 3 and 6 months, and borderline statistically significant at 12 months: aOR 1.64, 95%CI:1.30-2.29, p=0.001; 1.54, 95%CI:1.12-2.11, p=0.008; and 1.36, 95%CI:0.99-1.87, p=0.06, respectively. Stroke recurrence was similar between urban and non-urban settings at 3 and 6 months, but more likely in the non-urban setting at 12 months (aOR 1.94, 95%CI:1.14-3.29, p=0.014. In the non-urban setting, eligible patients were less likely to receive reperfusion therapy (aOR 0.5, 95%CI:0.28-0.91, p=0.023); acute stroke unit care was less consistently accessed (aOR 0.58, 95%CI:0.48-0.70, p Conclusion: This first comprehensive prospective NZ nationwide stroke study showed significant differences in stroke outcomes and access to key acute stroke interventions between urban and non-urban hospitals. This inequity requires urgent intervention from health system funders and providers.

Background: Non-urban hospitals often operate under greater resource constraints and less specialisation due to reduced economy of scale. We assessed whether access to stroke rehabilitation services is affected by hospital geographic location. In addition, we assessed the impact of specific rehabilitation interventions on patient outcomes. Methods: REGIONS Care is a New Zealand (NZ) nationwide prospective observational study with up to one-year follow-up exploring ethnic and geographic inequities in stroke care access and outcome. For this analysis, we compared rehabilitation outcomes and service access in urban versus non-urban hospital settings. The main outcome was favorable modified Rankin Scale of 0-2 at 3, 6, and 12 months. Outcomes were adjusted for age, stroke severity, pre-morbid function, and other potential confounders using multivariate logistic regression. Results: This cohort included 2379 patients with a confirmed diagnosis of stroke who were admitted to a NZ hospital between 1 May 2018 and 31 October 2018. There was no significant difference between geographic locations in access to inpatient services (OR=1.00; p=0.99) or reaching inpatient rehabilitation within seven days of admission (OR=1.16; p=0.32). Patients in non-urban areas had poorer access to intensive inpatient therapy (OR=0.54; p Conclusions: Patients admitted to non-urban hospital experience better IDT goal setting, but poorer access to community rehabilitation services and less intensive physical therapy during inpatient rehabilitation. Reduced therapy intensity resulted in a lower rate of functional independence at 3 months. These results will drive service improvements in the stroke rehabilitation space.

Background and Purpose— Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before tenecteplase thrombolysis for acute ischemic stroke. Methods— We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results— We identified 13 patients receiving intravenous tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69–85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4–21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57–113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0–2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions— Our experience suggests intravenous thrombolysis with tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.

Importance Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, setting, and participants Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main outcomes and measures The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and relevance Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial registration ClinicalTrials.gov Identifier: NCT03340493.

Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66).Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.None.

Background Stroke systems of care differ between larger urban and smaller rural settings and it is unclear to what extent this may impact on patient outcomes. Ethnicity influences stroke risk factors and care delivery as well as patient outcomes in nonstroke settings. Little is known about the impact of ethnicity on poststroke care, especially in Māori and Pacific populations. Objective Our goal is to describe the protocol for the Reducing Ethnic and Geographic Inequities to Optimise New Zealand Stroke Care (REGIONS Care) study. Methods This large, nationwide observational study assesses the impact of rurality and ethnicity on best practice stroke care access and outcomes involving all 28 New Zealand hospitals caring for stroke patients, by capturing every stroke patient admitted to hospital during the 2017-2018 study period. In addition, it explores current access barriers through consumer focus groups and consumer, carer, clinician, manager, and policy-maker surveys. It also assesses the economic impact of care provided at different types of hospitals and to patients of different ethnicities and explores the cost-efficacy of individual interventions and care bundles. Finally, it compares manual data collection to routine health administrative data and explores the feasibility of developing outcome models using only administrative data and the cost-efficacy of using additional manually collected registry data. Regarding sample size estimates, in Part 1, Study A, 2400 participants are needed to identify a 10% difference between up to four geographic subgroups at 90% power with an α value of .05 and 10% to 20% loss to follow-up. In Part 1, Study B, a sample of 7645 participants was expected to include an estimated 850 Māori and 419 Pacific patients and to provide over 90% and over 80% power, respectively. Regarding Part 2, 50% of the patient or carer surveys, 40 provider surveys, and 10 focus groups were needed to achieve saturation of themes. The main outcome is the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes include mRS scores; EQ-5D-3L (5-dimension, 3-level EuroQol questionnaire) scores; stroke recurrence; vascular events; death; readmission at 3, 6, and 12 months; cost of care; and themes around access barriers. Results The study is underway, with national and institutional ethics approvals in place. A total of 2379 patients have been recruited for Part 1, Study A; 6837 patients have been recruited for Part 1, Study B; 10 focus groups have been conducted and 70 surveys have been completed in Part 2. Data collection has essentially been completed, including follow-up assessment; however, primary and secondary analyses, data linkage, data validation, and health economics analysis are still underway. Conclusions The methods of this study may provide the basis for future epidemiological studies that will guide care improvements in other countries and populations. International Registered Report Identifier (IRRID) DERR1-10.2196/25374

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

Cough reflex testing has been evaluated as a component of the clinical swallowing assessment as a means of identifying patients at risk of aspiration during swallowing. A previous study by our research group found good sensitivity and specificity of the cough reflex test for identifying patients at risk of aspiration post-stroke, yet its use did not decrease pneumonia rates, contrary to previous reports. The aim of this study was to expand on our earlier work by implementing a clinical management protocol incorporating cough reflex testing within the same healthcare setting and compare patient outcomes to those from the original study and to evaluate clinical outcomes in patients with acute stroke who were managed using the Dysphagia in Stroke Protocol (DiSP). Secondarily, to compare those outcomes to historical data prior to implementation of the DiSP. This clinical audit measured outcomes from 284 patients with acute stroke managed per the DiSP, which guides use of videofluoroscopic swallowing study and patient management based on clinical exam with cough reflex testing. Data from our previous trial were included for comparison of pre- and post-DiSP patient outcomes. Data collection took place between November 2012 and April 2016 at four urban hospitals within New Zealand. Following implementation of the DiSP, the rate of aspiration pneumonia (10%) was substantially lower than the pre-DiSP rate (28%), with no pneumonia readmissions within 3 months. Pneumonia-related mortality was unchanged. By 3 months, 81% of the patients were on a normal diet and 67% had returned home, compared to pre-DiSP outcomes of 55% and 55% respectively. Previous work has suggested that simply implementing cough reflex testing in dysphagia management may not be sufficient to improve patient outcomes. The present study adds to this picture by suggesting that the true variable of influence may be the way in which the results of the test are applied to patient care. There is a strong case to support the use of a structured protocol if cough reflex testing is to be implemented in clinical practice.

IntroductionThe REGIONS Care study assesses stroke care throughout New Zealand. It includes a national audit and here we present organisational survey results assessing current availability of interventions and management approaches in each hospital.MethodsAll 20 District Health Boards were invited to complete a survey about patients managed per annum, care setting, and service provision. Results were grouped into rural and urban groups to assess for geographic differences.ResultsAll NZ hospitals managing stroke patients completed the survey. Results found that of these hospitals 92% have an acute stroke unit, 85% have a TIA pathway, but only 58% offer rapid access specialist TIA services. 100% offer thrombolysis, 92% use pre-hospital notification and rapid ED triage system, and 73% an in-hospital ‘code stroke’ alert. 50% have access to thrombectomy. Only 32% offer a dedicated inpatient stroke rehabilitation unit. While 92% provide community rehabilitation, only 11% offer early supported discharge programmes. 87% routinely provide stroke patient education, but only 54% provide individualised stroke care plans at discharge. Only 28% have access to a psychologist. In-hospital stroke alerts (p=0.014), access to thrombectomy (p=0.016), access to stroke unit care (p=0.027), and routine referral to stroke foundation (p=0.049) were more common in urban areas.ConclusionThe results of this organisational survey indicates that stroke care provision has improved since the last audit in 2009, but important gaps remain. These results will help services focus on specific areas for improvement, some of which such as pre-hospital alerts should be relatively easy to address.

Background and Purpose— Reliable predictors of hemorrhagic transformation (HT) after stroke thrombolysis have not been identified. We analyzed hemorrhage in a randomized trial of tissue plasminogen activator (t-PA) vs placebo in ischemic stroke patients. We hypothesized that acute diffusion-weighted imaging (DWI) lesion volumes would be larger and blood pressures would be higher in patients with HT. Methods— HT was assessed 2 to 5 days after treatment in 97 patients. Hemorrhage was assessed by using susceptibility-weighted imaging sequences and was classified as petechial hemorrhagic infarction (HI) or parenchymal hematoma (PH). Results— PH was more frequent in t-PA– (11/49) than in placebo- (4/48) treated patients ( P =0.049). Patients with PH had larger DWI lesion volumes (63.1±56.1 mL) than did those without HT (27.6±39.0 mL, P =0.033). There were no differences in baseline systolic blood pressure (SBP) between patients with and without hemorrhage. Weighted average SBP 24 hours after treatment was higher in patients with PH (159.4±18.8 mL, P Conclusions— Pretreatment DWI lesion volume and postthrombolysis BP are both predictive of HT. Consideration should be given to excluding patients with very large baseline DWI volumes from t-PA therapy and to more stringent BP control after stroke thrombolysis.

Summary Background Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3–6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). Methods We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3–6 h after onset of ischaemic stroke. PWI and DWI were done before and 3–5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. Findings We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71·6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1·24 with alteplase and 1·78 with placebo (ratio 0·69, 95% CI 0·38–1·28; Student's t test p=0·239); the median relative infarct growth was 1·18 with alteplase and 1·79 with placebo (ratio 0·66, 0·36–0·92; Wilcoxon's test p=0·054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0·001), better neurological outcome (p Interpretation Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. Funding National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; Heart Foundation of Australia.

Background and Purpose— The Alberta Stroke Program Early CT Score (ASPECTS) is a validated method of assessing parenchymal ischemic changes, including focal swelling and hypoattenuation. The hypothesis that these signs result from different pathophysiological processes was tested by comparing CT with diffusion and perfusion- weighted MRI. Methods— MRI and CT were performed, within 2 hours of each other, in 30 ischemic stroke patients Results— Isolated focal swelling was seen in 25 ASPECTS cortical regions from 6 patients. Cortical hypoattenuation was observed in 25 regions from 11 patients. Median relative apparent diffusion coefficient was significantly lower in hypoattenuated regions (0.84; interquartile range, 0.66 to 0.91) relative to those with focal swelling (0.97; interquartile range, 0.91 to 1.01; P P =0.002). Median relative cerebral blood volume was increased (121.1%; interquartile range, 112.0 to 130.3) in focal swelling regions, relative to normal-appearing tissue (94.7%; interquartile range, 62.0 to 114.6; P P =0.012). Infarction occurred in all hypoattenuated regions, but only in 32% of those with focal swelling. Conclusions— Elevated relative cerebral blood volume and normal relative apparent diffusion coefficient in ASPECTS regions with focal swelling on CT is consistent with penumbral tissue. Isolated focal swelling is not always associated with infarction. These results support removal of focal swelling from the ASPECTS system.

Background: Current guidelines for the treatment of acute ischemic stroke exclude patients with seizure at stroke onset from consideration for thrombolytic therapy. It may be difficult to differentiate an ischemic stroke from postictal Todd’s paralysis by clinical examination and noncontrast CT scan. Magnetic resonance imaging (MRI) with diffusion- (DWI) and perfusion-weighted images (PWI) and angiography (MRA) can be used to confirm the diagnosis of an acute ischemic process in the presence of concurrent seizures. Methods: A case report of a patient who presented with seizures, in whom the combination of DWI/PWI MRI and MRA confirmed the diagnosis of an embolic ischemic stroke. The patient was treated with intravenous recombinant tissue plasminogen activator with clinical and radiological improvement. Conclusions: Treatment decisions with regard to thrombolysis in acute stroke patients should be based on parameters of cerebral perfusion, assessment of collateral blood flow and presence of potentially salvageable tissue. Modern neuroimaging techniques that can rapidly assess these variables, such as DWI/PWI MRI and MRA, can improve the current selection of patients who are likely to benefit from thrombolysis and extend its benefit to patients who would otherwise be excluded, such as those with seizures at stroke onset.

Background and Purpose— Reperfusion and recanalization have both been used as surrogate markers of clinical outcome in trials of stroke thrombolysis. We aimed to prove that the beneficial impact of recanalization with intravenous tissue plasminogen activator on clinical outcomes is attributable to reperfusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). Methods— EPITHET was a prospective, randomized, placebo-controlled trial of intravenous tissue plasminogen activator in the 3- to 6-hour window. Reperfusion was defined as >90% reduction in magnetic resonance perfusion-weighted imaging lesion volume and recanalization as improvement of MR angiographic Thrombolysis In Myocardial Infarction grading by ≥2 points from baseline to Day 3 to 5. Results— At Day 3 to 5, reperfusion and recanalization with intravenous tissue plasminogen activator were strongly correlated. Reperfusion was associated with improved clinical outcome independent of whether recanalization occurred. In contrast, recanalization was not associated with clinical outcome when reperfusion was included as a covariate in regression analyses. Conclusion— Reperfusion is a surrogate marker of clinical outcomes independent of recanalization based on the criteria applied in EPITHET. The impact of recanalization on clinical outcomes was attributable to reperfusion.

Background and aim Treatment of ischemic stroke patients with tissue-type plasminogen activator (tPA) is known to be effective and cost-effective, yet the percentage of patients treated with thrombolysis in hospitals remains low. The purpose of this study is to examine whether providing thrombolysis in New Zealand hospitals is currently cost-effective and to estimate the amount that might be spent on campaigns aimed at increasing thrombolysis receipt rates. Methods A decision-analytic model was developed and populated using health services data from the literature and the Auckland Regional Community Stroke Outcome Study. The cost–utilities of providing thrombolysis over one-year and patient lifetime were estimated. Using a threshold of NZ$20 000 (US$15 337) per quality-adjusted life year, the analysis identified the maximum amount that might be spent on campaigns aiming to increase rates of receipt of thrombolysis above their current levels. Monte Carlo simulations and probabilistic sensitivity analysis explored the robustness of the findings. Results Providing thrombolysis was cost-effective, especially when long-term costs and effects were considered (NZ$6641 or US$5093 per quality-adjusted life year). The results suggest that better management within hospitals would be more effective in increasing thrombolysis receipt rates (up to 17%) than campaigns aiming at higher awareness of stroke symptoms in the community. The amount that might be spent on a national campaign to increase rate of receipt of thrombolysis from its current level (3% of eligible patients) depended upon the effectiveness of the campaign, ranging from under NZ$6 million for New Zealand for an increase in rate to 30% to over $9 million for an increase in rate to 50%. Conclusion While thrombolysis is a cost-effective treatment in New Zealand, resources should be devoted to campaigns, both within hospitals and in the community, to increase coverage.

We examined the impact of major earthquakes on acute stroke admissions by a retrospective review of stroke admissions in the 6 weeks following the 4 September 2010 and 22 February 2011 earthquakes. The control period was the corresponding 6 weeks in the previous year. In the 6 weeks following the September 2010 earthquake there were 97 acute stroke admissions, with 79 (81.4%) ischaemic infarctions. This was similar to the 2009 control period which had 104 acute stroke admissions, of whom 80 (76.9%) had ischaemic infarction. In the 6 weeks following the February 2011 earthquake, there were 71 stroke admissions, and 61 (79.2%) were ischaemic infarction. This was less than the 96 strokes (72 [75%] ischaemic infarction) in the corresponding control period. None of the comparisons were statistically significant. There was also no difference in the rate of cardioembolic infarction from atrial fibrillation between the study periods. Patients admitted during the February 2011 earthquake period were less likely to be discharged directly home when compared to the control period (31.2% versus 46.9%, p=0.036). There was no observable trend in the number of weekly stroke admissions between the 2 weeks leading to and 6 weeks following the earthquakes. Our results suggest that severe psychological stress from earthquakes did not influence the subsequent short term risk of acute stroke, but the severity of the earthquake in February 2011 and associated civil structural damages may have influenced the pattern of discharge for stroke patients.

Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion.We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups.Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p0.00001 in some studies with n10. Of 32 patients taking bezafibrate, 20 had abnormal (97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p0.00001). In elderly (65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013).Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.

Background and Purpose— The influence of stroke lateralization on functional and cardiovascular outcome after stroke is not well established. We evaluated the influence of hemispheric lateralization among patients enrolled in prospective acute stroke trials. Methods— We obtained data from the VISTA database for acute stroke trials which reported lateralization. Baseline data, cardiac adverse events, and 90-day outcomes were compared between right and left hemisphere stroke patients. A “hemisphere unbiased” subscore of the NIHSS which omitted items strongly associated with lateralized cognitive deficits was also compared for trials which reported individual NIHSS item scores. A multivariable analysis of outcome predictors was performed. Results— Three acute stroke trials met the prespecified inclusion criteria. 1644 placebo-treated patients with documented hemispheric lateralization were included in the analysis. Baseline NIHSS was higher for left hemisphere patients (mean 16.2, versus 12.8 right, P P =0.49). There was no difference between hemispheres in 90-day modified Rankin Score (3.43 left, 3.29 right, P =0.13), mortality (22.1% left, 19.5% right, P =0.20), or cardiac adverse events ( P =0.71). Hemispheric lateralization was not an independent predictor of outcome in the multivariable analysis after controlling for the hemispheric bias intrinsic to the NIHSS. Conclusions— There is no difference in functional outcome between patients with right or left hemisphere stroke. Use of the baseline NIHSS score to predict stroke outcome must take hemispheric lateralization into account. Stroke lateralization is not an important predictor of cardiac adverse events or 90-day mortality.

Insula infarction is an early computed tomographic sign of middle cerebral artery (MCA) territory stroke and may affect cardiovascular autonomic function.To determine insula involvement in MCA territory infarction and its relationship with infarcts in the remainder of the MCA territory, stroke severity, and clinically relevant cardiovascular conditions.Case series (August 1, 1997, to June 30, 2000).Academic stroke center.A total of 150 consecutive patients with nonlacunar MCA territory stroke who underwent magnetic resonance imaging within 48 hours of stroke onset.Association of insula infarction with the National Institutes of Health Stroke Scale (NIHSS) score, location of vascular occlusion, and cardiovascular events.Insular lesions were present in 72 patients (48%); 34 (23%) had major insular lesions and 38 (25%) had minor lesions. Insula infarction was associated with lenticulostriate territory infarction (46% vs 14%; P.001), more than one third of MCA territory infarction (35% vs 3%; P.001), higher NIHSS score (13.5 vs 6; P.001), and proximal vascular occlusion detected on magnetic resonance angiography. These associations were strongest for patients with major insular lesions. Clinically significant new arrhythmia was present in 15 of 72 with insula infarction (13 atrial fibrillations) and 4 of 78 without (P = .06). Insula infarction was associated with lower diastolic blood pressure at admission but was not associated with pulse rate, QTc interval, myocardial infarction, or sudden death.The insular cortex is involved in almost half of patients with nonlacunar ischemic MCA territory strokes. Major insula involvement is associated with large MCA territory infarcts, proximal MCA occlusions, and greater stroke severity. Insula infarction was not a predictor of clinically significant acute cardiovascular events during hospital stay in our patients.

Background and Purpose— The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)–diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Methods— Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWI vol -DWI vol ) and DWI expansion (T2 Day 90-vol -DWI Acute-vol ) were also assessed. Results— Mean age was 68±11, time to MRI 4.5±0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps ( P R =−0.51; P =0.009). Conclusions— Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

Background and Purpose — Hemorrhagic transformation (HT) is a potentially dangerous complication of thrombolytic therapy. Recent studies suggest that diffusion-weighted MRI (DWI) can help to predict the risk of intracerebral hemorrhage (ICH) after thrombolysis. We sought to examine which pretreatment DWI parameters and clinical data are predictive of ICH after intravenous thrombolysis. Methods — We retrospectively reviewed our prospective stroke database for patients with ischemic stroke treated with intravenous recombinant tissue plasminogen activator (rtPA) within 3 hours from symptom onset who had DWI before treatment and MRI with T2* sequence or CT 24 to 48 hours later to assess for ICH over the past 4 years. We measured the volumes and voxel-by-voxel apparent diffusion coefficient (ADC) values of the initial DWI lesions and retrieved demographic data, risk factors, National Institutes of Health Stroke Scale (NIHSS) scores on admission, and blood tests results. We examined several variables using univariate and multivariate regression analyses to determine predictors of ICH. Results — Twenty-nine patients fulfilled our inclusion criteria; 17 patients (58%) had ICH, and of these 4 (13%) had symptomatic ICH and fatal outcome. On univariate analysis, higher systolic blood pressure, NIHSS score, serum glucose level, volume of initial DWI lesion, and absolute number of voxels with ADC value ≤550×10 −6 mm 2 /s were statistically associated with ICH, and all were subjected to multivariate analysis. However, only the absolute number of voxels, ie, volume of ischemic tissue on DWI, with ADC ≤550×10 −6 mm 2 /s emerged as an independent predictor of ICH. Conclusions — Our findings suggest that volumetric ADC analysis can be used to assess ICH risk after thrombolysis. This may be particularly helpful if rtPA is to be given outside the 3-hour window.

Background and Purpose — Time of stroke onset is uncertain for patients who wake from sleep with stroke. Functional imaging techniques may allow estimation of benefit and risk of acute stroke therapy. We compared the clinical and multimodal MRI findings of patients with uncertain stroke onset with those with known onset time. Methods — Patients imaged within 24 hours of ischemic stroke onset between January 1997 and June 2000 were identified from a prospective stroke registry. Clinical and imaging data from patients with known stroke onset (group I) were compared with those who woke with stroke (group II). Results — A total of 364 patients were identified, of whom 100 (27%) woke from sleep with stroke. Group I and group II did not differ in age, gender, National Institutes of Health Stroke Scale, or TOAST (Trial of Org 10172 in Acute Stroke Treatment) diagnoses. Time from stroke onset was shorter in group I (mean 6.0 versus 13.3 hours, P P =0.004) and time from stroke onset (β=−0.238, P =0.031) in multivariate analysis. The mean ADC of group II patients was lower than that of group I patients within 3 hours of stroke detection (mean 556 versus 665 μm 2 /s, P 2 /s, in addition to a DWI-PWI mismatch pattern. Conclusions — Onset time is uncertain in over one quarter of acute ischemic stroke patients. Clinical features of these patients do not differ significantly from those with known onset time. Some patients who wake with stroke seem to have favorable imaging characteristics for acute stroke therapy. Further study is needed to determine whether criteria for therapy based on imaging parameters can safely be applied to these patients.

Background and Purpose — The National Institutes of Health Stroke Scale (NIHSS) is an established measure of neurological impairment; however, it can award more points for tests of presumed left-hemisphere function, such as language, than for tests of right-hemisphere function, such as neglect. This difference may be important if a low NIHSS score is used to exclude patients with right-hemisphere stroke from clinical trials or established treatments. The aim of this study was to investigate whether the relationship between acute NIHSS score and acute stroke volume as determined by acute diffusion- and perfusion-weighted MRI (DWI and PWI) differs between right- and left-sided stroke. Methods — This was a retrospective study of 153 patients with acute stroke seen at Beth Israel Deaconess Medical Center between January 1995 and March 2000 who underwent an MRI examination and NIHSS within 24 hours of stroke onset. NIHSS score was recorded prospectively by the admitting stroke fellow at the time of acute presentation, immediately preceding imaging. Computerized volumetric analysis of the MRI lesions was performed by investigators blinded to clinical data. Results — There were significant correlations between the acute NIHSS scores and acute DWI lesion volumes ( r =0.48 right, r =0.58 left) and between acute NIHSS scores and perfusion-weight imaging hypoperfusion volumes ( r =0.62 right, r =0.60 left). For patients with NIHSS scores of 0 to 5, the DWI volume of right cerebral lesions was greater than that of left-sided lesions (mean volume, 8.8 versus 3.2 cm 3 ; P =0.04). Among patients with DWI lesions larger than the median volume (9 cm 3 ), 8 of 37 with right-sided stroke had an NIHSS score of 0 to 5 compared with 1 of 39 patients with left-sided stroke ( P =0.01). Multiple linear regression analysis revealed a significantly lower acute NIHSS on the right compared with the left side when adjusted for stroke volume on chronic T2 imaging ( P =0.03). Conclusions — Patients with right-sided stroke may have a low NIHSS score despite substantial DWI lesion volume. Acute imaging information, such as that available with multimodal MRI, may be useful to identify patients for inclusion in acute stroke protocols when there is clinical uncertainty about eligibility. Prospective evaluation of criteria incorporating acute imaging data is required.

Background Magnetic resonance (MR) signal changes suggestive of cerebral venous thrombosis (CVT) on T1- and T2-weighted images may be subtle and their identification requires a high degree of suspicion. Magnetic resonance venography remains essential for definitive diagnosis. Recent reports have shown that T2 * -weighted MR sequence is more sensitive than T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) images in detecting subarachnoid and intracerebral hemorrhages, both of which can be seen in association with CVT. The value of T2 * -weighted magnetic resonance imaging (MRI) in diagnosing CVT has not been well studied. Objectives To investigate and describe T2 * (susceptibility-weighted) MRI findings in 5 patients with CVT. Methods We reviewed our stroke database from May 1, 1997, through May 31, 2001. The diagnosis of CVT was made in 6 patients, 5 had an MRI with T2* sequence. We examined T2 * /susceptibility-weighted images for these 5 patients to determine their ability, relative to T1-weighted, T2-weighted, and FLAIR sequences, to detect CVT. Results On T2 * -weighted images, we were able to detect areas of hypointensities in the affected veins and/or sinuses in all 5 patients. Thrombosed veins and/or sinuses were more easily seen on T2 * -weighted images than on any other MR sequence. The T2 * sequence also allowed visualization of associated hemorrhagic venous infarcts, which were considerably less obvious on other MR sequences. Conclusions The T2 * -weighted MR sequence can be useful in rapid detection of CVT and may enable the diagnosis to be made prior to MR venography. This is particularly important in clinically unsuspected patients, in whom MR venography is rarely obtained.