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Background: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent. Methods: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www.ClinicalTrials.gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase. Results: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65–1.23]; I 2 =0%). Among patients treated with low dose (2 =0%), 0.77 ([95% CI, 0.53–1.14]; I 2 =0%), and 2.31 ([95% CI, 0.69–7.75]; I 2 =40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%–3.49%]; I 2 =0%, 7 studies), 1.69% ([95% CI, 1.14%–2.32%]; I 2 =1%, 23 studies), and 4.19% ([95% CI, 1.92%–7.11%]; I 2 =52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents. Conclusions: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.

Background: Although geographical differences in treatment and outcomes after stroke have been described, we lack evidence on differences in the costs of treatment between urban and nonurban regions. Additionally, it is unclear whether greater costs in one setting are justified given the outcomes achieved. We aimed to compare costs and quality-adjusted life years in people with stroke admitted to urban and nonurban hospitals in New Zealand. Methods: Observational study of patients with stroke admitted to the 28 New Zealand acute stroke hospitals (10 in urban areas) recruited between May and October 2018. Data were collected up to 12 months poststroke including treatments in hospital, inpatient rehabilitation, other health service utilization, aged residential care, productivity, and health-related quality of life. Costs in New Zealand dollars were estimated from a societal perspective and assigned to the initial hospital that patients presented to. Unit prices for 2018 were obtained from government and hospital sources. Multivariable regression analyses were conducted when assessing differences between groups. Results: Of 1510 patients (median age 78 years, 48% female), 607 presented to nonurban and 903 to urban hospitals. Mean hospital costs were greater in urban than nonurban hospitals ($13 191 versus $11 635, P =0.002), as were total costs to 12 months ($22 381 versus $17 217, P P Conclusions: Better outcomes following initial presentation to urban hospitals were associated with greater costs compared to nonurban hospitals. These findings may inform greater targeted expenditure in some nonurban hospitals to improve access to treatment and optimize outcomes.

Background and ObjectivesEndovascular thrombectomy (EVT) for large vessel occlusion ischemic stroke is either performed under general anesthesia (GA) or with non-GA techniques such as conscious sedation or local anesthesia alone. Previous small meta-analyses have demonstrated superior recanalization rates and improved functional recovery with GA when compared with non-GA techniques. The publication of further randomized controlled trials (RCTs) could provide updated guidance when choosing between GA and non-GA techniques.MethodsA systematic search for trials in which stroke EVT patients were randomized to GA or non-GA was performed in Medline, Embase, and the Cochrane Central Register of Controlled Trials. A systematic review and meta-analysis using a random-effects model was performed.ResultsSeven RCTs were included in the systematic review and meta-analysis. These trials included a total of 980 participants (GA, N = 487; non-GA, N = 493). GA improves recanalization by 9.0% (GA 84.6% vs non-GA 75.6%; odds ratio [OR] 1.75, 95% CI 1.26–2.42,p= 0.0009), and the proportion of patients with functional recovery improves by 8.4% (GA 44.6% vs non-GA 36.2%; OR 1.43, 95% CI 1.04–1.98,p= 0.03). There was no difference in hemorrhagic complications or 3-month mortality.DiscussionIn patients with ischemic stroke treated with EVT, GA is associated with higher recanalization rates and improved functional recovery at 3 months compared with non-GA techniques. Conversion to GA and subsequent intention-to-treat analysis will underestimate the true therapeutic benefit. GA is established as effective in improving recanalization rates in EVT (7 Class 1 studies) with a high Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) certainty rating. GA is established as effective in improving functional recovery at 3 months in EVT (5 Class 1 studies) with a moderate GRADE certainty rating. Stroke services need to develop pathways to incorporate GA as the first choice for most EVT procedures in acute ischemic stroke with a level A recommendation for recanalization and level B recommendation for functional recovery.

Background: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0–2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. Methods: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). Results: There were 131 patients; the median age was 64 [53–74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12–22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1–3] versus 3 [1–6] in the patients selected with noncontrast CT+CT angiography, P =0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01–0.19]; P Conclusions: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Active conductive head cooling is a simple and non-invasive intervention that may slow infarct growth in ischemic stroke. We investigated the effect of active conductive head cooling on brain temperature using whole brain echo-planar spectroscopic imaging. A cooling cap (WElkins Temperature Regulation System, 2nd Gen) was used to administer cooling for 80 minutes to healthy volunteers and chronic stroke patients. Whole brain echo-planar spectroscopic imaging scans were obtained before and after cooling. Brain temperature was estimated using the Metabolite Imaging and Data Analysis System software package, which allows voxel-level temperature calculations using the chemical shift difference between metabolite (N-acetylaspartate, creatine, choline) and water resonances. Eleven participants (six healthy volunteers, five post-stroke) underwent 80 ± 5 minutes of cooling. The average temperature of the coolant was 1.3 ± 0.5°C below zero. Significant reductions in brain temperature (ΔT = –0.9 ± 0.7°C, P = 0.002), and to a lesser extent, rectal temperature (ΔT = –0.3 ± 0.1°C, P = 0.03) were observed. Exploratory analysis showed that the occipital lobes had the greatest reduction in temperature (ΔT = –1.5 ± 1.2°C, P = 0.002). Regions of infarction had similar temperature reductions to the contralateral normal brain. Future research could investigate the feasibility of head cooling as a potential neuroprotective strategy in patients being considered for acute stroke therapies.

BackgroundWe describe the first-in-human experience using the Route 92 Medical Aspiration System to perform thrombectomy in the initial 45 consecutive stroke patients enrolled in the SUMMIT NZ trial. This aspiration system includes a specifically designed delivery catheter which enables delivery of 0.070 inch and 0.088 inch aspiration catheters.MethodsThe SUMMIT NZ trial is a prospective, multicenter, single-arm study with core lab imaging adjudication. Patients presenting with acute ischemic stroke from large vessel occlusion are eligible to enrol. The study has had three phases which transitioned from use of the 0.070 inch to the 0.088 inch catheter.ResultsVessel occlusions were located in the internal carotid artery (27%), M1 (60%) and M2 (13%). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 10). Across the three phases, the first-pass reperfusion rate of modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b was 62% using the Route 92 Medical system; this rate was 29% in phase 1, 56% in phase 2, and 80% in phase 3. The first-pass reperfusion rate of mTICI ≥2c was 42% overall, 29% in phase 1, 33% in phase 2, and 55% in phase 3. A final reperfusion rate of mTICI ≥2b was achieved in 96% of cases, with 36% of cases using adjunctive devices. Patients had an average improvement of 6.7 points in NIHSS from baseline at 24 hours, and at 90 days 48% were functionally independent (modified Rankin Scale 0–2).ConclusionsIn this early experience, the Route 92 Medical Aspiration System has been effective and safe. The system has design features that improve catheter deliverability and have the potential to increase first-pass reperfusion rates in aspiration thrombectomy.

It is important to understand how consumers (person with stroke/family member/carer) and health workers perceive stroke care services.Consumers and health workers from across New Zealand were surveyed on perceptions of stroke care, access barriers, and views on service centralisation. Quantitative data were summarised using descriptive statistics whilst thematic analysis was used for free-text answers.Of 149 consumers and 79 health workers invited to complete a survey, 53 consumers (36.5%) and 41 health workers (51.8%) responded. Overall, 40/46 (87%) consumers rated stroke care as 'good/excellent' compared to 24/41 (58.6%) health workers. Approximately 72% of consumers preferred to transfer to a specialised hospital. We identified three major themes related to perceptions of stroke care: 1) 'variability in care by stage of treatment'; 2) 'impact of communication by health workers on care experience'; and 3) 'inadequate post-acute services for younger patients'. Four access barrier themes were identified: 1) 'geographic inequities'; 2) 'knowing what is available'; 3) 'knowledge about stroke and available services'; and 4) 'healthcare system factors'.Perceptions of stroke care differed between consumers and health workers, highlighting the importance of involving both in service co-design. Improving communication, post-hospital follow-up, and geographic equity are key areas for improvement.Implications for rehabilitationProvision of detailed information on stroke recovery and available services in the community is recommended.Improvements in the delivery of post-hospital stroke care are required to optimise stroke care, with options including routine phone follow up appointments and wider development of early supported discharge services.Stroke rehabilitation services should continue to be delivered 'close to home' to allow community integration.Telehealth is a likely enabler to allow specialist urban clinicians to support non-urban clinicians, as well as increasing the availability and access of community rehabilitation.

ObjectiveTo evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature.MethodsSearches were performed using MEDLINE, Embase, and Cochrane databases for studies that compared EVT with EVT with adjunctive IAT (EVT + IAT). Safety outcomes included symptomatic intracerebral hemorrhage and mortality at 3 months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b–3) and functional independence, defined as a modified Rankin Scale score of 0–2 at 3 months.ResultsFive studies were identified that compared combined EVT + IAT (IA alteplase or urokinase) with EVT only and were included in the random-effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT + IAT and 1,424 patients receiving EVT only. Pooled analysis did not demonstrate any differences between EVT + IAT and EVT only in rates of symptomatic intracerebral hemorrhage (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.20–1.85;p= 0.78), mortality (OR: 0.77, 95% CI: 0.54–1.10;p= 0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52–2.15;p= 0.89). There was a higher rate of functional independence in patients treated with EVT + IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00–1.80;p= 0.053).ConclusionAdjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intra-arterial alteplase or urokinase as rescue therapy during EVT.

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.

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.

This study assessed stroke reperfusion treatments trends in 2019 and 2020 with comparison back to 2015. Additional analyses looked at differences by sex and ethnicity.The National Stroke Register contains data on all stroke patients who received reperfusion therapies since 2015. Outcomes included treatment rates, delays, mortality and complications by year, sex, and ethnicity. Continuous variables were compared using the Wilcoxon Rank-Sum Test and presented as p-values. Rate-based results were compared using incidence rate comparison and presented as p-values +/- 95% confidence intervals.In 2020, 11.3% (828/7333) received intravenous thrombolysis (IVT) and 5.5% (404/7333) underwent stroke clot retrieval (SCR), increasing from 6.5% (389/5963) and 0.5% (30/5963) in 2015, respectively. Among reperfused patients (IVT, SCR, both), 8.3% had died at seven days and 3.0% (29/959) experienced sICH. Door-to-treatment time was stable between 2019 and 2020, with median (IQR) of 61 (44-84) and 61 (41-87) minutes, respectively. Initial presentation to a SCR centre was associated with shorter onset-to-reperfusion time of 286 (206-566) minutes, compared with 403 (295-550) minutes (p0.001). While onset-to-door time was shorter for Māori (72 (44-112) minutes, p0.001) and Pacific patients (70 (48-105) minutes, p=0.03) compared with NZ Europeans, door-to-needle time was longer in Māori (66 (48-88) compared to 59 (41-83) minutes (p=0.001). Female (73.7+/15.3 years) patients were on average 4.4 years older than males (69.3+/-14.6 years) and less likely to receive thrombolysis (12.7% vs 14.9%, p=0.02).Reperfusion therapy rates continue to rise, now driven by increasing rates of SCR. Longer door-to-needle time in Māori and lower reperfusion rates in women require further exploration and attention.

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

Stroke is a leading cause of death and disability worldwide with many people left with impaired motor function. Evidence from experimental animal models of stroke indicates that reducing motor cortex inhibition may facilitate neural plasticity and motor recovery. This study compared primary motor cortex (M1) inhibition measures over the first 12 wk after stroke with a cohort of age-similar healthy controls. The excitation-inhibition ratio and gamma-aminobutyric acid (GABA) neurotransmission within M1 were assessed using magnetic resonance spectroscopy and threshold hunting paired-pulse transcranial magnetic stimulation respectively. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Patients with a functional corticospinal pathway had motor-evoked potentials on the paretic side and exhibited better recovery from upper limb impairment and recovery of function than patients without a functional corticospinal pathway. Compared with age-similar controls, the neurochemical balance in terms of the excitation-inhibition ratio was greater within contralesional M1 in patients with a functional corticospinal pathway. There was evidence for elevated long-interval inhibition in both ipsilesional and contralesional M1 compared with controls. Short-interval inhibition measures differed between the first and second phases, with evidence for elevation of the former only in ipsilesional M1 and no evidence of disinhibition for the latter. Overall, findings from transcranial magnetic stimulation indicate an upregulation of GABA-mediated tonic inhibition in M1 early after stroke. Therapeutic approaches that aim to normalize inhibitory tone during the subacute period warrant further investigation.NEW & NOTEWORTHY Magnetic resonance spectroscopy indicated higher excitation-inhibition ratios within motor cortex during subacute recovery than age-similar healthy controls. Measures obtained from adaptive threshold hunting paired-pulse transcranial magnetic stimulation indicated greater tonic inhibition in patients compared with controls. Therapeutic approaches that aim to normalize motor cortex inhibition during the subacute stage of recovery should be explored.

Over 80% of patients exhibit an acute increase in blood pressure (BP) following stroke. Current clinical guidelines make no distinction in BP management between patients with or without prior hypertension. Spontaneously hypertensive (SH) rats were preinstrumented with telemeters to record BP, intracranial pressure, and brain tissue oxygen in the predicted ischemic penumbra for 3 days before and 10 days after transient middle cerebral artery occlusion (n=8 per group) or sham (n=5). Before stroke, BP was either left untreated or chronically treated to a normotensive level (enalapril 10 mg/kg per day). Poststroke elevations in BP were either left uncontrolled, controlled (to the prestroke baseline level), or overcontrolled (to a normotensive level) via subcutaneous infusion of labetalol. Baseline values of intracranial pressure and brain tissue oxygen were similar between all groups, whereas BP was lower in treated SH rats (144±3 versus 115±5 mm Hg; P P =0.005) and treated SH rats (+13±5 mm Hg; P =0.021). Intervening to prevent BP from increasing after stroke did not worsen outcome. However, reducing BP below prestroke baseline levels was associated with higher intracranial pressure (days 1–3; P P

Background: Ethnic differences in post-stroke outcomes have been largely attributed to biological and socioeconomic characteristics resulting in differential risk factor profiles and stroke subtypes, but evidence is mixed. Aims: This study assessed ethnic differences in stroke outcome and service access in New Zealand (NZ) and explored underlying causes in addition to traditional risk factors. Methods: This national cohort study used routinely collected health and social data to compare post-stroke outcomes between NZ Europeans, Māori, Pacific Peoples, and Asians, adjusting for differences in baseline characteristics, socioeconomic deprivation, and stroke characteristics. First and principal stroke public hospital admissions during November 2017 to October 2018 were included (N = 6879). Post-stroke unfavorable outcome was defined as being dead, changing residence, or becoming unemployed. Results: In total, 5394 NZ Europeans, 762 Māori, 369 Pacific Peoples, and 354 Asians experienced a stroke during the study period. Median age was 65 years for Māori and Pacific Peoples, and 71 and 79 years for Asians and NZ Europeans, respectively. Compared with NZ Europeans, Māori were more likely to have an unfavorable outcome at all three time-points (odds ratio (OR) = 1.6 (95% confidence interval (CI) = 1.3–1.9); 1.4 (1.2–1.7); 1.4 (1.2–1.7), respectively). Māori had increased odds of death at all time-points (1.7 (1.3–2.1); 1.5 (1.2–1.9); 1.7 (1.3–2.1)), change in residence at 3 and 6 months (1.6 (1.3–2.1); 1.3 (1.1–1.7)), and unemployment at 6 and 12 months (1.5 (1.1–2.1); 1.5 (1.1–2.1)). There was evidence of differences in post-stroke secondary prevention medication by ethnicity. Conclusion: We found ethnic disparities in care and outcomes following stroke which were independent of traditional risk factors, suggesting they may be attributable to stroke service delivery rather than patient factors.

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

Registration Australian New Zealand Clinical Trials Registry: ACTRN12619001274167p Rationale Cerebral blood flow is blood pressure-dependent when cerebral autoregulation is impaired. Cerebral ischemia and anesthetic drugs impair cerebral autoregulation. In ischemic stroke patients treated with endovascular thrombectomy, induced hypertension is a plausible intervention to increase blood flow in the ischemic penumbra until reperfusion is achieved. This could potentially reduce final infarct size and improve functional recovery. Aim To test if patients with large vessel occlusion stroke treated with endovascular thrombectomy will benefit from induced hypertension. Design Prospective, randomized, parallel group, open label, multicenter clinical trial with blinded assessment of outcomes. Procedures Patients with anterior circulation stroke treated with endovascular thrombectomy with general anesthesia within 6 h of symptom onset, and patients with ‘wake up’ stroke or presenting within 6 to 24 h with potentially salvageable tissue on computed tomography perfusion scanning, are included. Participants are randomized to a systolic blood pressure target of 140 mmHg or 170 mmHg from procedure initiation until recanalization. Methods to maintain the blood pressure are at the discretion of the procedural anesthesiologist. Study outcomes The primary efficacy outcome is improvement in disability measured by modified Rankin Scale score at 90 days. The primary safety outcome is all-cause mortality at 90 days. Analysis The Mann-Whitney U test will be used to test the ordinal shift in the seven-category modified Rankin Scale score. All-cause mortality will be estimated using the Kaplan-Meier method and compared using a log-rank test.

Background: Depression and anxiety are the two most frequently studied emotional outcomes of stroke. However, few previous studies have been carried out at a population level or beyond 6 months post stroke. The aim of this study was to describe depression and anxiety across the first year following incident ischemic stroke (IS), and identify predictive factors in a population-based study. Method: The Hospital Anxiety Depression Scale (HADS) was administered at baseline (within 2 weeks of onset), and again at 1-month, 6-months and 12-months after IS in a sample (N = 365) drawn from a population-based study. Results: Over 75% of those assessed experienced depression or anxiety symptoms below cut-offs for probable disorder across the year post stroke. Moderate to severe symptoms for anxiety were approximately twice as likely (range 4.1%–10.6%) as compared to depression (range 2.5%–5.0%) at each assessment. The greatest improvement in anxiety occurred within the first month post stroke. In contrast, the greatest reduction in depression occurred between 1- to 6-months post stroke. Conclusions: Anxiety symptoms in the moderate to severe range were twice as common as depression, and improved over the first month post stroke, whilst depression symptoms persisted for up to 6 months, indicating a need to target these two issues at different points in the recovery process.

Highlights • MRI metrics can classify MEP status with 81% accuracy using support vector machine. • Metrics from both T1 and diffusion MRI are important for this classification. • Machine learning is a powerful tool for analysing multivariate MRI data., Background Motor outcomes after stroke can be predicted using structural and functional biomarkers of the descending corticomotor pathway, typically measured using magnetic resonance imaging and transcranial magnetic stimulation, respectively. However, the precise structural determinants of intact corticomotor function are unknown. Identifying structure–function links in the corticomotor pathway could provide valuable insight into the mechanisms of post-stroke motor impairment. This study used supervised machine learning to classify upper limb motor evoked potential status using MRI metrics obtained early after stroke. Methods Retrospective data from 91 patients (49 women, age 35–97 years) with moderate to severe upper limb weakness within a week after stroke were included in this study. Support vector machine classifiers were trained using metrics from T1- and diffusion-weighted MRI to classify motor evoked potential status, empirically measured using transcranial magnetic stimulation. Results Support vector machine classification of motor evoked potential status was 81% accurate, with false positives more common than false negatives. Important structural MRI metrics included diffusion anisotropy asymmetry in the supplementary and pre-supplementary motor tracts, maximum cross-sectional lesion overlap in the sensorimotor tract and ventral premotor tract, and mean diffusivity asymmetry in the posterior limbs of the internal capsule. Interpretations MRI measures of corticomotor structure are good but imperfect predictors of corticomotor function. Residual corticomotor function after stroke depends on both the extent of cross-sectional macrostructural tract damage and preservation of white-matter microstructural integrity. Analysing the corticomotor pathway using a multivariable MRI approach across multiple tracts may yield more information than univariate biomarker analyses.

Background and ObjectivesInternational evidence shows that patients treated at nonurban hospitals experience poorer access to key stroke interventions. Evidence for whether this results in poorer outcomes is conflicting and generally based on administrative or voluntary registry data. The aim of this study was to use prospective high-quality comprehensive nationwide patient-level data to investigate the association between hospital geography and outcomes of patients with stroke and access to best-practice stroke care in New Zealand.MethodsThis is a prospective, multicenter, nationally representative observational study involving all 28 New Zealand acute stroke hospitals (18 nonurban) and affiliated rehabilitation and community services. Consecutive adults admitted to the hospital with acute stroke between May 1 and October 31, 2018, were captured. Outcomes included functional outcome (modified Rankin Scale [mRS] score shift analysis), functional independence (mRS score 0–2), quality of life (EuroQol 5-dimension, 3-level health-related quality of life questionnaire), stroke/vascular events, and death at 3, 6, and 12 months and proportion accessing thrombolysis, thrombectomy, stroke units, key investigations, secondary prevention, and inpatient/community rehabilitation. Results were adjusted for age, sex, ethnicity, stroke severity/type, comorbid conditions, baseline function, and differences in baseline characteristics.ResultsOverall, 2,379 patients were eligible (mean [SD] age 75 [13.7] years; 51.2% male; 1,430 urban, 949 nonurban). Patients treated at nonurban hospitals were more likely to score in a higher mRS score category (greater disability) at 3 (adjusted odds ratio [aOR] 1.28, 95% CI 1.07–1.53), 6 (aOR 1.33, 95% CI 1.07–1.65), and 12 (aOR 1.31, 95% CI 1.06–1.62) months and were more likely to have died (aOR 1.57, 95% CI 1.17–2.12) or experienced recurrent stroke and vascular events at 12 months (aOR 1.94, 95% CI 1.14–3.29 and aOR 1.65, 95% CI 1.09–2.52). Fewer nonurban patients received recommended stroke interventions, including endovascular thrombectomy (aOR 0.25, 95% CI 0.13–0.49), acute stroke unit care (aOR 0.60, 95% CI 0.49–0.73), antiplatelet prescriptions (aOR 0.72, 95% CI 0.58–0.88), ≥60 minutes of daily physical therapy (aOR 0.55, 95% CI 0.40–0.77), and community rehabilitation (aOR 0.69, 95% CI 0.56–0.84).DiscussionPatients managed at nonurban hospitals experience poorer stroke outcomes and reduced access to key stroke interventions across the entire care continuum. Efforts to improve access to high quality stroke care in nonurban hospitals should be a priority.

Background The choice of anesthetic technique for ischemic stroke patients undergoing endovascular thrombectomy is controversial. Intravenous propofol and volatile inhalational general anesthetic agents have differing effects on cerebral hemodynamics, which may affect ischemic brain tissue and clinical outcome. We compared outcomes in patients undergoing endovascular thrombectomy with general anesthesia who were treated with propofol or volatile agents. Methods Consecutive endovascular thrombectomy patients treated using general anesthesia were identified from our prospective database. Baseline patient characteristics, anesthetic agent, and clinical outcomes were recorded. Functional independence at 3 months was defined as a modified Rankin Scale of 0 to 2. Results There were 313 patients (182 [58.1%] men; mean±SD age, 64.7±15.9 y; 257 [82%] anterior circulation), of whom 254 (81%) received volatile inhalational (desflurane or sevoflurane), and 59 (19%) received intravenous propofol general anesthesia. Patients with propofol anesthesia had more ischemic heart disease, higher baseline National Institutes of Health Stroke Scale scores, more basilar artery occlusion, and were less likely to be treated with intravenous thrombolysis. Multivariable logistic regression analysis showed that propofol anesthesia was associated with improved functional independence at 3 months (odds ratio=2.65; 95% confidence interval, 1.14-6.22; P=0.03) and a nonsignificant trend toward reduced 3-month mortality (odds ratio=0.37; 95% CI, 0.12-1.10; P=0.07). Conclusion In stroke patients undergoing endovascular thrombectomy treated using general anesthesia, there may be a differential effect between intravenous propofol and volatile inhalational agents. These results should be considered hypothesis-generating and be tested in future randomized controlled trials.

Objective To evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular clot retrieval (ECR) in ischaemic stroke, we performed a systematic review and meta-analysis of the literature. Methods Searches were performed using Medline, Embase, and Cochrane databases for studies that compared ECR to ECR with adjunctive IAT (ECR+IAT). Safety outcomes included symptomatic intracerebral haemorrhage (sICH) and mortality at three months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b to 3), and functional independence, defined as a modified Rankin Scale score of 0 to 2 at three months. Results Five studies were identified that compared combined ECR+IAT (IA alteplase or urokinase) to ECR-only, and were included in the random effects meta-analysis. There were 1693 ECR patients, including 269 patients treated with combined ECR+IAT and 1424 patients receiving ECR-only. Pooled analysis did not demonstrate any differences between ECR+IAT and ECR-only in rates of sICH (OR: 0.61, 95% CI: 0.20-1.85; P=0.78), mortality (OR: 0.77, 95% CI: 0.54-1.10; P=0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52-2.15; P=0.89). There was a higher rate of functional independence in patients treated with ECR+IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00-1.80; P=0.053). Conclusions Adjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intraarterial alteplase or urokinase as rescue therapy during ECR.

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

Background: In New Zealand, Māori and Pacific people have higher age-adjusted stroke incidence rates, younger age at first stroke, and higher mortality at 12 months than other ethnic groups. We aimed to determine if access to acute stroke reperfusion therapy with intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT) is equitable among ethnic groups. Methods: Data were obtained from the Northern Region component of the New Zealand Stroke Registry over the 21 months between January 1, 2018 and September 30, 2019. Data recorded included demographic details, self-identified ethnicity, treatment times, and clinical outcomes. National hospital discharge coding of patients admitted with ischemic stroke and stroke unspecified was used to determine the proportion of patients treated by ethnic group. Results: There were 537 patients normally resident in the Northern Region who received reperfusion therapy: 281 received IVT alone, 123 received EVT after bridging IVT, and 133 received EVT alone. Of the 537 patients treated with IVT or EVT, there were 81 (15.1%) Māori, 78 (14.5%) Pacific, 57 (10.6%) Asian, and 341 (63.5%) NZ European/other ethnicity patients. There were no ethnic differences in treatment process times. When compared with NZ European/others, Māori and Pacific people were younger, and Māori had worse neurological impairment at admission. A higher proportion of Māori were treated with EVT with a trend to higher proportion treated with IVT. Day 90 modified Rankin Scale (mRS) for EVT-treated patients was similar apart from Asian patients who had worse outcome when compared with NZ European/others (mRS 3 vs. 2; p = 0.03). Conclusions: This study has shown equitable access to acute stroke reperfusion therapies and largely similar outcomes in different ethnic groups in northern New Zealand.

Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. Results. Short-interval intracortical inhibition was similar between patients and controls ( P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls ( P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function ( P = .002 and P = .017). GABA concentration was lower within ipsilesional ( P = .009) and contralesional ( P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

Rationale Rapid response by health-care systems for transient ischemic attack and minor stroke (TIA/mS) is recommended to maximize the impact of secondary prevention strategies. The applicability of this evidence to Australian non-hospital-based TIA/mS management is uncertain. Aims Within an Australian community setting we seek to document processes of care, establish determinants of access to care, establish attack rates and determinants of recurrent vascular events and other clinical outcomes, establish the performance of ABC2-risk stratification, and compare the processes of care and outcomes to those in the UK and New Zealand for TIA/mS. Sample size estimates Recruiting practices containing approximately 51 full-time-equivalent general practitioners to recruit 100 TIA/mS per year over a four-year study period will provide sufficient power for each of our outcomes. Methods and design An inception cohort study of patients with possible TIA/mS recruited from 16 general practices in the Newcastle-Hunter Valley-Manning Valley region of Australia. Potential TIA/mS will be ascertained by multiple overlapping methods at general practices, after-hours collaborative, and hospital in-patient and outpatient services. Participants’ index and subsequent clinical events will be adjudicated as TIA/mS or mimics by an expert panel. Study outcomes Process outcomes—whether the patient was referred for secondary care; time from event to first patient presentation to a health professional; time from event to specialist acute-access clinic appointment; time from event to brain and vascular imaging and relevant prescriptions. Clinical outcomes—recurrent stroke and major vascular events; and health-related quality of life. Discussion Community management of TIA/mS will be informed by this study.

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 and Objective. The likelihood of regaining independent walking after stroke is of concern to patients and their families and influences hospital discharge planning. The objective of this study was to explore factors that could be combined in an algorithm for predicting whether and when a patient will walk independently after stroke. Methods. Adults with new lower limb weakness were recruited within 3 days of having a stroke. Clinical assessment, transcranial magnetic stimulation, and magnetic resonance imaging were completed 1 to 2 weeks poststroke. Classification and regression tree (CART) analysis was used to identify factors that predicted whether a patient achieved independent walking by 6 or 12 weeks, or remained dependent at 12 weeks. Results. We recruited 41 patients (24 women; median age 72 years, range 43-96 years). The CART analysis results were used to create the Time to Walking Independently after STroke (TWIST) algorithm, which made accurate predictions for 95% of patients. Patients with a trunk control test score >40 at 1 week walked independently within 6 weeks. Patients with a trunk control test score

Background and Purpose— Several clinical measures and biomarkers are associated with motor recovery after stroke, but none are used to guide rehabilitation for individual patients. The objective of this study was to evaluate the implementation of upper limb predictions in stroke rehabilitation, by combining clinical measures and biomarkers using the Predict Recovery Potential (PREP) algorithm. Methods— Predictions were provided for patients in the implementation group (n=110) and withheld from the comparison group (n=82). Predictions guided rehabilitation therapy focus for patients in the implementation group. The effects of predictive information on clinical practice (length of stay, therapist confidence, therapy content, and dose) were evaluated. Clinical outcomes (upper limb function, impairment and use, independence, and quality of life) were measured 3 and 6 months poststroke. The primary clinical practice outcome was inpatient length of stay. The primary clinical outcome was Action Research Arm Test score 3 months poststroke. Results— Length of stay was 1 week shorter for the implementation group (11 days; 95% confidence interval, 9–13 days) than the comparison group (17 days; 95% confidence interval, 14–21 days; P =0.001), controlling for upper limb impairment, age, sex, and comorbidities. Therapists were more confident ( P =0.004) and modified therapy content according to predictions for the implementation group ( P Conclusions— PREP algorithm predictions modify therapy content and increase rehabilitation efficiency after stroke without compromising clinical outcome. Clinical Trial Registration— URL: http://anzctr.org.au . Unique identifier: ACTRN12611000755932.

Background and Purpose— In ischemic stroke, body temperature is associated with functional outcome. However, the relationship between temperature and outcome may differ in the intraischemic and postischemic phases of stroke. We aimed to determine whether body temperature before or after endovascular thrombectomy (EVT) for large vessel occlusion stroke is associated with clinical outcomes. Methods— Consecutive EVT patients were identified from a prospective registry. Temperature measurements within 24 hours of admission were stratified into pre-EVT (preprocedural and intraprocedural) and post-EVT measurements, which served as surrogates for the intraischemic and postischemic phases of large vessel occlusion stroke, respectively. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0, 1, or 2 at 3 months. Secondary outcomes included the ordinal shift of modified Rankin Scale scores at 3 months, symptomatic intracerebral hemorrhage, and mortality at 3 months. Results— Four hundred thirty-two participants were included (59% men, mean±SD age 65.6±15.7 years). Multivariable logistic regression demonstrated that higher median pre-EVT temperature (per 1°C increase) was an independent predictor of reduced functional independence (odds ratio [OR], 0.66 [95% CI, 0.46–0.94]; P =0.02), poorer modified Rankin Scale scores (common OR, 1.42 [95% CI, 1.08–1.85]; P =0.01), and increased mortality (OR, 1.65 [95% CI, 1.02–2.69]; P =0.04). Peak post-EVT temperature (per 1°C increase) was a significant predictor of elevated modified Rankin Scale scores (common OR, 1.39 [95% CI, 1.03–1.90]; P =0.03) and higher mortality (OR, 1.66 [95% CI, 1.04–2.67]; P =0.03). Conclusions— In patients with large vessel occlusion stroke treated with EVT, higher body temperatures during both the intraischemic and postischemic phases were associated with poorer clinical outcomes. Future research investigating the maintenance of normothermia or therapeutic hypothermia in patients needing to be transferred from primary to EVT-capable stroke centers could be considered.

Background and Purpose: Methods of identifying ischemic stroke patients with a greater probability of poor outcome following endovascular thrombectomy (EVT) might improve shared treatment decision-making between patients, families and physicians. Visually-graded cerebral atrophy is associated with worse functional outcome following EVT. We used an objective, automated method to measure cerebral atrophy and investigated whether this was associated with functional outcome in EVT patients. Methods: Consecutive EVT patients from a single-center registry were studied. CT brain scans were segmented with a combination of a validated U-Net and Hounsfield unit thresholding. Intracranial cerebrospinal fluid (CSF) volume was used as a marker of cerebral atrophy and calculated as a proportion of total intracranial volume. The primary outcome was functional independence, defined as a 3-month modified Rankin Scale (mRS) score of 0-2. Results: 360 EVT patients were included. Functional independence was achieved in 204 (56.7%) patients. The mean±SD CSF volume was 9.0±4.7% of total intracranial volume. Multivariable regression demonstrated that increasing CSF volume was associated with reduced functional independence (OR=0.65 per 5% increase in CSF volume; 95% CI, 0.48- 0.89; P=0.007) and higher 3-month mRS scores (common OR=1.59 per 5% increase in CSF volume; 95% CI, 1.05-2.41; P=0.03). Conclusions: Cerebral atrophy determined by automated measurement of intracranial CSF volume is associated with functional outcome in patients undergoing EVT. If validated in future studies, this simple, objective, and automated imaging marker could potentially be incorporated into decision-support tools in order to improve shared treatment decision making.

Background and Objectives: Chronic kidney disease (CKD) is present in 20% to 35% of acute ischemic stroke patients and may increase the risk of poor functional outcome or death. We aimed to determine whether CKD was associated with worse outcome in stroke patients treated with endovascular thrombectomy (EVT). Design, Setting, Participants, and Measurements: Consecutive EVT patients were identified from a prospective registry and dichotomized into patients with and without CKD, defined as an eGFR of less than 60 mL/min/1.73m2. The primary outcome was 3-month mortality following EVT. Secondary outcomes included symptomatic intracerebral hemorrhage (defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study), early neurological recovery (defined as change in National Institutes of Health Stroke Scale [NIHSS] score of ≥8 at 24 hours or an NIHSS of 0-1 at 24 hours) and functional independence (defined as a modified Rankin Scale [mRS] score of 0, 1 or 2) at 3 months. Results: 378 EVT patients (223 men; mean ± SD age 65 ± 15 years) were included. The median (IQR) admission eGFR was 71 (58-89) mL/min/1.73 m² and 117 (31%) patients had CKD. Multiple logistic regression adjusted for potential confounders demonstrated that CKD was a significant predictor of lower rates of functional independence (OR = .54, 95% CI, .31 to .90, P = .02), higher mRS scores (common OR = 1.78, 95% CI, 1.14 to 2.81, P = .01), and increased mortality (OR = 2.19, 95% CI, 1.16 to 4.12, P = .01). There was no association between CKD and early neurological recovery (OR = .92, 95% CI, .55 to 1.49, P = .71) or symptomatic intracerebral hemorrhage (OR = 1.18, 95% CI, .38 to 3.69, P = .77). Conclusions: CKD was a significant predictor of worse functional outcome and mortality in stroke patients treated with EVT. The presence of CKD should not preclude patients from proceeding to EVT, but may help with prognostication and improve shared decision-making between patients, families and physicians.

Aim: The goal of this paper is to provide a protocol for conducting a fifth population-based Auckland Regional Community Stroke study (ARCOS V) in New Zealand. Methods and Discussion: In this study, for the first time globally, (1) stroke and TIA burden will be determined using the currently used clinical and tissue-based definition of stroke, in addition to the WHO clinical classifications of stroke used in all previous ARCOS studies, as well as more advanced criteria recently suggested for an “ideal” population-based stroke incidence and outcomes study; and (2) age, sex, and ethnic-specific trends in stroke incidence and outcomes will be determined over the last four decades, including changes in the incidence of acute cerebrovascular events over the last decade. Furthermore, information at four time points over a 40-year period will allow the assessment of effects of recent changes such as implementation of the FAST campaign, ambulance pre-notification, and endovascular treatment. This will enable more accurate projections for health service planning and delivery. Conclusion: The methods of this study will provide a foundation for future similar population-based studies in other countries and populations.

Background In ischemic stroke patients, studies have suggested that clinical outcomes following endovascular thrombectomy are worse after general anesthesia (GA) compared with conscious sedation (CS). Most data are from observational trials, which are prone to measure and unmeasure confounding. We performed a systematic review and meta-analysis of thrombectomy trials where patients were randomized to GA or CS, and compared efficacy and safety outcomes. Methods The Medline, Embase, and Cochrane databases were searched for randomized controlled trials comparing GA to CS in endovascular thrombectomy. Efficacy outcomes included successful recanalization (Thrombolysis in Cerebral Infarction score of 2b to 3), and good functional outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included intracerebral hemorrhage and 3-month mortality. Results Four studies were identified and included in the random effects meta-analysis. Patients treated with GA achieved a higher proportion of successful recanalization (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.26-3.62; P=0.005) and good functional outcome (OR: 1.71, 95% CI: 1.13-2.59; P=0.01). For every 7.9 patients receiving GA, one more achieved good functional outcome compared with those receiving CS. There were no significant differences in intracerebral hemorrhage (OR: 0.61, 95% CI: 0.20-1.85; P=0.38) or 3-month mortality (OR: 0.62, 95% CI: 0.33-1.17; P=0.14) between GA and CS patients. Conclusions In centers with high quality, specialized neuroanesthesia care, GA treated thrombectomy patients had superior recanalization rates and better functional outcome at 3 months than patients receiving CS.

BACKGROUND Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) can help reverse stroke symptoms in selected patients but are both time sensitive interventions. AIMS To report current stroke reperfusion rates and quality measures as well as trends over time in New Zealand. METHOD Since 2015 New Zealand treatment centres have been mandated to enter prospectively all IVT and EVT patients into a low-cost National Stroke Register. Data were cleaned, and missing data added where possible through contact with individual hospitals. Main outcomes include treatment delays, vital status at day 7 and complications. RESULTS In 2018, there were 719 of 7173 (10.0%) patients with ischaemic stroke or stroke unspecified treated with IVT, up from 389 of 5963 (6.5%) patients in 2015 (P

Characteristics of patient’s drawings have been linked to short-term health-related outcomes across a range of health conditions. This study examined associations between brain drawings at 1 month and illness perceptions and post-concussion symptoms at 4 years in 92 adults following mild traumatic brain injury. Greater damage depicted at 1 month was correlated with perceived greater impact on life, duration of injury, symptoms of brain injury, emotional consequences and late-onset post-concussion symptoms. Results indicate that brain drawings shortly after traumatic brain injury offer a simple and insightful tool that may help to identify those who need additional support to improve long-term outcomes.

Background. The PREP2 algorithm combines clinical and neurophysiological measures to predict upper-limb (UL) motor outcomes 3 months poststroke, using 4 prediction categories based on Action Research Arm Test (ARAT) scores. The algorithm was accurate at 3 months for 75% of participants in a previous validation study. Objective. This study aimed to evaluate whether PREP2 predictions made at baseline are correct 2 years poststroke. We also assessed whether patients’ UL performance remained stable, improved, or worsened between 3 months and 2 years after stroke. Methods. This is a follow-up study of 192 participants recruited and assessed in the original PREP2 validation study. Participants who completed assessments 3 months poststroke (n = 157) were invited to complete follow-up assessments at 2 years poststroke for the present study. UL outcomes were assessed with the ARAT, upper extremity Fugl-Meyer Scale, and Motor Activity Log. Results. A total of 86 participants completed 2-year follow-up assessments in this study. PREP2 predictions made at baseline were correct for 69/86 (80%) participants 2 years poststroke, and PREP2 UL outcome category was stable between 3 months and 2 years poststroke for 71/86 (83%). There was no difference in age, stroke severity, or comorbidities among patients whose category remained stable, improved, or deteriorated. Conclusions. PREP2 algorithm predictions made within days of stroke are correct at both 3 months and 2 years poststroke for most patients. Further investigation may be useful to identify which patients are likely to improve, remain stable, or deteriorate between 3 months and 2 years.

The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging.We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline.After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days.Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

BackgroundIn ischemic stroke, increased glycated hemoglobin (HbA1c) and glucose levels are associated with worse outcome following thrombolysis, and possibly, endovascular thrombectomy.ObjectiveTo evaluate the association between admission HbA1c and glucose levels and outcome following endovascular thrombectomy.MethodsConsecutive patients treated with endovascular thrombectomy with admission HbA1c and glucose levels were included. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0–2 at 3 months. Secondary outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3), early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) score ≥8 points, or NIHSS score of 0–1 at 24 hours), symptomatic intracerebral hemorrhage (sICH), and mortality at 3 months.Results223 patients (136 (61%) men; mean±SD age 64.5±14.6) were included. The median (IQR) HbA1c and glucose were 39 (36-45) mmol/mol and 6.9 (5.8–8.4) mmol/L, respectively. Multiple logistic regression analysis demonstrated that increasing HbA1c levels (per 10 mmol/mol) were associated with reduced functional independence (OR=0.76; 95% CI 0.60–0.96; p=0.02), increased sICH (OR=1.33; 95% CI 1.03 to 1.71; p=0.03), and increased mortality (OR=1.26; 95% CI 1.01 to 1.57; p=0.04). There were no significant associations between glucose levels and outcome measures (all p>0.05).ConclusionsHbA1c levels are an independent predictor of worse outcome following endovascular thrombectomy. The addition of HbA1c to decision-support tools for endovascular thrombectomy should be evaluated in future studies.