Publications by authors named "Timothy J Kleinig"

49 Publications

Global impact of COVID-19 on stroke care.

Int J Stroke 2021 Mar 29:1747493021991652. Epub 2021 Mar 29.

Neurology, Grady Memorial Hospital, Emory University, Atlanta, Georgia, USA.

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.

Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).

Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.

Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.

Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.
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http://dx.doi.org/10.1177/1747493021991652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010375PMC
March 2021

Utility of Severity-Based Prehospital Triage for Endovascular Thrombectomy: ACT-FAST Validation Study.

Stroke 2021 01 22;52(1):70-79. Epub 2020 Dec 22.

Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital (H.Z., L.C., J.L.N., C.W., F.A., F.N., P.J.M., M.W.P., N.Y., S.M.D., B.C.V.C.), University of Melbourne, Australia.

Background And Purpose: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm.

Methods: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening.

Results: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0-61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region.

Conclusions: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.
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http://dx.doi.org/10.1161/STROKEAHA.120.031467DOI Listing
January 2021

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Association of Reperfusion After Thrombolysis With Clinical Outcome Across the 4.5- to 9-Hours and Wake-up Stroke Time Window: A Meta-Analysis of the EXTEND and EPITHET Randomized Clinical Trials.

JAMA Neurol 2021 Feb;78(2):236-240

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Importance: Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain.

Objective: To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials.

Design, Setting, And Participants: Individual patient meta-analysis of randomized clinical trials performed from August 2001 to June 2018 with 3-month follow-up. Patients had acute ischemic stroke with 4.5-to 9-hours poststroke onset or with wake-up stroke were randomized to alteplase or placebo after perfusion mismatch imaging. Analysis began July 2019 and ended May 2020.

Exposures: Reperfusion was defined as more than 90% reduction in time to maximum of more than 6 seconds' lesion volume at 24- to 72-hour follow-up.

Main Outcomes And Measures: Ordinal logistic regression adjusted for baseline age and National Institutes of Health Stroke Scale score was used to analyze functional improvement in day 90 modified Rankin Scale score overall, including a reperfusion × time-to-randomization multiplicative interaction term, and in the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with a National Institutes of Health Stroke Scale score increase of 4 points or more.

Results: Reperfusion was assessable in 270 of 295 patients (92%), 68 of 133 (51%) in the alteplase group, and 38 of 137 (28%) in the placebo reperfused group (P < .001). The median (interquartile range) age was 76 (66-81) years in the reperfusion group vs 74 (64.5-81.0) years in the group with no reperfusion. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (7-15) in the reperfusion group vs 12 (8.0-17.5) in the no reperfusion group. Overall, reperfusion was associated with improved functional outcome (common odds ratio, 7.7; 95% CI, 4.6-12.8; P < .001). Reperfusion was associated with significantly improved functional outcome in each of the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata, with no evidence of association between time to randomization and beneficial effect of reperfusion (P = .63). Symptomatic hemorrhage, assessed in all 294 patients, occurred in 3 of 51 (5.9%) in the 4.5- to 6-hours group, 2 of 28 (7.1%) in the 6- to 9-hours group, and 4 of 73 (5.5%) in the wake-up stroke in patients treated with alteplase (Fisher P = .91).

Conclusions And Relevance: Strong benefits of reperfusion in all time strata without differential risk in symptomatic hemorrhage support the consistent treatment effect of alteplase in perfusion mismatch-selected patients throughout the 4.5- to 9-hours and wake-up stroke time window.
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http://dx.doi.org/10.1001/jamaneurol.2020.4123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607491PMC
February 2021

Stroke incidence and subtypes in Aboriginal people in remote Australia: a healthcare network population-based study.

BMJ Open 2020 10 8;10(10):e039533. Epub 2020 Oct 8.

Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

Objectives: We aimed to compare the incidence, subtypes and aetiology of stroke, and in-hospital death due to stroke, between Aboriginal and non-Aboriginal people in Central Australia, a remote region of Australia where a high proportion Aboriginal people reside (40% of the population). We hypothesised that the rates of stroke, particularly in younger adults, would be greater in the Aboriginal population, compared with the non-Aboriginal population; we aimed to elucidate causes for any identified disparities.

Design: A retrospective population-based study of patients hospitalised with stroke within a defined region from 1 January 2011 to 31 December 2014.

Setting: Alice Springs Hospital, the only neuroimaging-capable acute hospital in Central Australia, serving a network of 50 healthcare facilities covering 672 000 km.

Participants: 161 residents (63.4% Aboriginal) of the catchment area admitted to hospital with stroke.

Primary And Secondary Outcome Measures: Rates of first-ever stroke, overall (all events) stroke and in-hospital death.

Results: Of 121 residents with first-ever stroke, 61% identified as Aboriginal. Median onset-age (54 years) was 17 years younger in Aboriginal patients (p<0.001), and age-standardised stroke incidence was threefold that of non-Aboriginal patients (153 vs 51 per 100 000, incidence rate ratio 3.0, 95% CI 2 to 4). The rate ratios for the overall rate of stroke (first-ever and recurrent) were similar. In Aboriginal patients aged <55 years, the incidence of ischaemic stroke was 14-fold greater (95% CI 4 to 45), and intracerebral haemorrhage 19-fold greater (95% CI 3 to 142) than in non-Aboriginal patients. Crude prevalence of diabetes mellitus (70.3% vs 34.0%, p<0.001) and hypercholesterolaemia (68.9% vs 51.1%, p=0.049) was greater, and age-standardised in-hospital deaths were fivefold greater (35 vs 7 per 100 000, 95% CI 2 to 11) in Aboriginal patients than in non-Aboriginal patients.

Conclusions: Stroke incidence (both subtypes) and in-hospital deaths for remote Aboriginal Australians are dramatically greater than in non-Aboriginal people, especially in patients aged <55 years.
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http://dx.doi.org/10.1136/bmjopen-2020-039533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545633PMC
October 2020

Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke.

Stroke 2020 12 7;51(12):3681-3689. Epub 2020 Oct 7.

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital (L.C., N.Y., B.Y., M.W.P., G.A.D., S.M.D., B.C.V.C.), University of Melbourne, Parkville, Australia.

Background And Purpose: Tenecteplase improved functional outcomes and reduced the requirement for endovascular thrombectomy in ischemic stroke patients with large vessel occlusion in the EXTEND-IA TNK randomized trial. We assessed the cost-effectiveness of tenecteplase versus alteplase in this trial.

Methods: Post hoc within-trial economic analysis included costs of index emergency department and inpatient stroke hospitalization, rehabilitation/subacute care, and rehospitalization due to stroke within 90 days. Sources for cost included key study site complemented by published literature and government websites. Quality-adjusted life-years were estimated using utility scores derived from the modified Rankin Scale score at 90 days. Long-term modeled cost-effectiveness analysis used a Markov model with 7 health states corresponding to 7 modified Rankin Scale scores. Probabilistic sensitivity analyses were performed.

Results: Within the 202 patients in the randomized controlled trial, total cost was nonsignificantly lower in the tenecteplase-treated patients (40 997 Australian dollars [AUD]) compared with alteplase-treated patients (46 188 AUD) for the first 90 days(=0.125). Tenecteplase was the dominant treatment strategy in the short term, with similar cost (5412 AUD [95% CI, -13 348 to 2523]; =0.181) and higher benefits (0.099 quality-adjusted life-years [95% CI, 0.001-0.1967]; =0.048), with a 97.4% probability of being cost-effective. In the long-term, tenecteplase was associated with less additional lifetime cost (96 357 versus 106 304 AUD) and greater benefits (quality-adjusted life-years, 7.77 versus 6.48), and had a 100% probability of being cost-effective. Both deterministic sensitivity analysis and probabilistic sensitivity analyses yielded similar results.

Conclusions: Both within-trial and long-term economic analyses showed that tenecteplase was highly likely to be cost-effective for patients with acute stroke before thrombectomy. Recommending the use of tenecteplase over alteplase could lead to a cost saving to the healthcare system both in the short and long term. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388061.
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http://dx.doi.org/10.1161/STROKEAHA.120.029666DOI Listing
December 2020

Antithrombotic Treatment of Embolic Stroke of Undetermined Source: RE-SPECT ESUS Elderly and Renally Impaired Subgroups.

Stroke 2020 06 14;51(6):1758-1765. Epub 2020 May 14.

Department of Neurology, Evangelisches Klinikum Bethel, Bielefeld, Germany (W.-R.S.).

Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.
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http://dx.doi.org/10.1161/STROKEAHA.119.028643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379165PMC
June 2020

Dabigatran Reversal Before Intravenous Tenecteplase in Acute Ischemic Stroke.

Stroke 2020 05 25;51(5):1616-1619. Epub 2020 Mar 25.

From the Department of Neurology, Christchurch Hospital, New Zealand (J.B., J.N.F., D.W., T.Y.W.).

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.
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http://dx.doi.org/10.1161/STROKEAHA.119.028327DOI Listing
May 2020

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

Lancet 2020 03 20;395(10227):878-887. Epub 2020 Feb 20.

McMaster University, Hamilton, ON, Canada.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018.

Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups.

Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.

Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.
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http://dx.doi.org/10.1016/S0140-6736(20)30258-0DOI Listing
March 2020

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

JAMA 2020 04;323(13):1257-1265

Department of Medicine, Ballarat Base Hospital, Ballarat, Victoria, Australia.

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.
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http://dx.doi.org/10.1001/jama.2020.1511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139271PMC
April 2020

Stroke unit legislation-Mandating a uniform standard of care?

Int J Stroke 2020 02 29;15(2):NP6-NP7. Epub 2020 Jan 29.

Stroke Research Programme, Discipline of Medicine, University of Adelaide, Adelaide, Australia.

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http://dx.doi.org/10.1177/1747493020903516DOI Listing
February 2020

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.

BMJ Open 2019 11 14;9(11):e031144. Epub 2019 Nov 14.

Neurology Department, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Introduction: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.

Methods And Analysis: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.

Ethics And Dissemination: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
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http://dx.doi.org/10.1136/bmjopen-2019-031144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887075PMC
November 2019

Determining the optimal dose of tenecteplase before endovascular therapy for ischemic stroke (EXTEND-IA TNK Part 2): A multicenter, randomized, controlled study.

Int J Stroke 2020 Jul 30;15(5):567-572. Epub 2019 Sep 30.

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.

Background And Hypothesis: Intravenous thrombolysis with tenecteplase is more effective than alteplase in achieving substantial reperfusion at initial angiographic assessment and improves functional outcome. However, the optimal dose of tenecteplase remains uncertain. We hypothesized that 0.40 mg/kg tenecteplase is superior to 0.25 mg/kg tenecteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy.

Study Design: EXTEND-IA TNK part 2 is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale (mRS)≤3 (no upper age limit), absence of contraindications to intravenous thrombolysis, and large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal CT. Patients are randomized to IV tenecteplase at either 0.40 mg/kg (max 40 mg) or 0.25 mg/kg (max 25 mg) prior to thrombectomy.

Study Outcomes: The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified Treatment In Cerebral Infarction (mTICI) 2b/3, or the absence of retrievable intracranial thrombus. Secondary outcomes include mRS at day 90 and early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration: ClinicalTrials.gov NCT03340493.
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July 2020

A Modular Hybrid Exoskeletal-Soft Glove for High Degree of Freedom Monitoring Capability.

IEEE Int Conf Rehabil Robot 2019 06;2019:577-582

In this paper, we present a hybrid exoskeletal-soft glove for the application of on-axis angle sensors that can be placed close to the center of rotation of the digit joints. 3D printed exoskeletal digit segments that run medially on most digits connect to low friction bearings. Exoskeletal segments and bearings provide rigid fixation points for a variety of traditional angle sensors, while a combination of textile and rigid structure fixate exoskeletal digits to the digits and hand. Exoskeletal digits are designed modularly so that only required digits are used and to reduce difficulty in donning and doffing. On-axis measurement may prove useful in control or assessment tasks in rehabilitation. The articulation of the digits while wearing the glove is demonstrated, albeit without sensors, showing little restriction at an early stage of the design process. Exoskeletal metacarpophalangeal joints of the 3rd and 4th digits require more work as the flexion/extension joint axis is inaccessible and moves when he digits are articulated. The proposed device must be customized for an individual and will facilitate an alternative approach to existing hand posture monitoring techniques.
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http://dx.doi.org/10.1109/ICORR.2019.8779488DOI Listing
June 2019

Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.

Lancet 2019 07 22;394(10193):139-147. Epub 2019 May 22.

Department of Neurology, Sapienza University of Roma, Rome, Italy.

Background: 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.

Methods: 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.

Findings: 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).

Interpretation: 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.

Funding: None.
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July 2019

Response to Late-Window Endovascular Revascularization Is Associated With Collateral Status in Basilar Artery Occlusion.

Stroke 2019 May 16:STROKEAHA118023361. Epub 2019 May 16.

From the Department of Medicine and Neurology, University of Melbourne, Parkville, Australia (F. Alemseged, D.S., B.Y., G.S., M.W.P., S.M.D., N.Y., B.C.V.C.).

Background and Purpose- The benefit of endovascular therapy in extended time windows has been demonstrated in patients with anterior circulation large vessel occlusion ischemic stroke and favorable imaging profile. We evaluated whether collaterals and thrombus burden influence the associations between revascularization, time-to-treatment, and outcome in endovascular therapy-treated patients with basilar artery occlusion. Methods- We retrospectively analyzed clinical and imaging data of consecutive endovascular therapy-treated patients with basilar artery occlusion included in the multicenter Basilar Artery Treatment and Management Collaboration. The BATMAN (Basilar Artery on Computed Tomography Angiography score, which evaluates thrombus burden and collaterals) and the PC-CS (Posterior Circulation Collateral score, which evaluates collaterals) were assessed on computed tomography angiography, blinded to clinical outcome. Good outcome was defined as modified Rankin Scale score of ≤3 within 3 months; revascularization (successful reperfusion) as modified Thrombolysis in Cerebral Infarction 2b-3 (or TIMI [Thrombolysis In Myocardial Infarction] 2-3 in the BASICS [Basilar Artery International Cooperation Study] registry). Results- We included 172 patients with basilar artery occlusion treated with endovascular therapy (124 with mechanical thrombectomy): mean (SD) age 65 (13) years, median National Institutes of Health Stroke Scale 22 (interquartile range 12-30), 64 (37%) treated >6 hours. Revascularization (achieved in 79% of patients) was associated with good outcome ( P=0.003). The use of new generation thrombectomy devices was associated with good outcome ( P=0.03). In patients who achieved revascularization, 29/46 (63%) of patients with a favorable BATMAN score and 26/51 (51%) with favorable PC-CS had good outcomes. In logistic regression analysis (adjusted for age, National Institutes of Health Stroke Scale, and time-to-treatment ≤6/>6 hours), revascularization was associated with good outcome in patients with favorable BATMAN score (odds ratio, 15.8; 95% CI, 1.4-175; P=0.02) or PC-CS (odds ratio, 9.4; 95% CI, 1.4-64; P=0.02). In patients who achieved revascularization, early (time-to-treatment ≤6 hours) but not late treatment was associated with improved outcome in patients with unfavorable BATMAN score (18/52 [35%]; odds ratio, 15; 95% CI, 1.9-124; P=0.01) or PC-CS (16/44 [36%]; odds ratio, 5.5; 95% CI, 1.4-21; P=0.01). Conclusions- Revascularization is associated with good outcome in patients with basilar artery occlusion with good collaterals and less extensive occlusion, even >6 hours after onset.
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May 2019

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

N Engl J Med 2019 05;380(19):1795-1803

From Florey Institute of Neuroscience and Mental Health (H.M., L. Churilov, N.Y., V.T., L. Carey, A.M., G.A.D.), the Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital (B.C.V.C., M.W.P., L. Churilov, S. Christensen, N.Y., G.S., A.B., B.Y., A.M., S.M.D., G.A.D.), and the Department of Radiology, Royal Melbourne Hospital (P.M.D., B.Y., P.J.M.), University of Melbourne, Parkville, the Department of Medicine, School of Clinical Science, Monash University, Clayton (H.M., T.G.P.), the Departments of Medicine and Neurology, Melbourne Medical School, University of Melbourne and Western Health, Sunshine Hospital, St. Albans (T.W.), the Department of Neurosciences, Eastern Health and Eastern Health Clinical School, Monash University, Box Hill (H.M.D., C.F.B.), the Department of Neurology, University Hospital Geelong, Deakin University, Geelong (B.C.), the Department of Neurology, Austin Hospital, Austin Health, Heidelberg (V.T.), and Occupational Therapy, School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora (L. Carey), VIC, the Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital (C.R.L., F.M.), University of Newcastle (J.S.), Newcastle, the Department of Neurology, Westmead Hospital (N.M.), the Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney (M.K.), and the Department of Neurology, St. Vincent's Hospital Sydney (R.M.), Sydney, and the Department of Neurology, Gosford Hospital, Gosford (J.S.), NSW, the Department of Neurology, Royal Adelaide Hospital (T.J.K., J.J.), the Department of Neurology, Lyell McEwin Hospital (D.F.), and the Department of Neurology, Queen Elizabeth Hospital (J.J.), Adelaide, SA, the Department of Medicine, Sunshine Coast University Hospital, Nambour (R.G.), the Department of Neurology, Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane (A.A.W.), and the Department of Neurology, Gold Coast University Hospital, Southport (A.S.), and Australia and Griffith University, Gold Coast (A.S.), QLD - all in Australia; the Graduate Institute of Clinical Medical Science (C.H.) and the School of Medicine (C.-H.T.), China Medical University, and the Department of Neurology, China Medical University Hospital (C.-H.T.), Taichung, the Department of Neurology, Tri-Service General Hospital, National Defense Medical Center (J.-T.L.), the Department of Neurology, Shuang Ho Hospital (C.-J.H.), the Department of Neurology, En Chu Kong Hospital (Y.S.), the Stroke Center and Department of Neurology, National Taiwan University Hospital (J.-S.J.), and the Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei Medical University College of Medicine (L.-M.L.), Taipei, the Stroke Center and Department of Neurology, Changhua Christian Hospital, Changhua (M.-C.S.), the Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan (C.-H.C.), and the Department of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung (C.-H.L.) - all in Taiwan; the Department of Neurology, Helsinki University Hospital, Helsinki (S. Curtze, A.M.); the Department of Neurology, Auckland City Hospital, University of Auckland, Auckland, New Zealand (P.A.B.); and the Stanford Stroke Center, Stanford University, Stanford, CA (S. Christensen).

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.).
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http://dx.doi.org/10.1056/NEJMoa1813046DOI Listing
May 2019

Influence of occlusion site and baseline ischemic core on outcome in patients with ischemic stroke.

Neurology 2019 06 1;92(23):e2626-e2643. Epub 2019 May 1.

From the Department of Neurology (H.T., M.W.P., C.R.L., L.L., N.J.S., A.B.), John Hunter Hospital, University of Newcastle, Australia; Department of Medical Imaging, Division of Neuroradiology (R.I.A.), Sunnybrook Health Sciences Center and University of Toronto; Division of Neurology, Department of Medicine (K.S.B.), University of Alberta, Edmonton, Canada; Department of Neurology (M.L.), the Second Affiliated Hospital of Zhejiang University, Hangzhou, China; and Department of Neurology (T.J.K.), Royal Adelaide Hospital, Australia.

Objective: We assessed patient clinical outcomes based on occlusion location, focusing on distal occlusions to understand if occlusion location was an independent predictor of outcome, and tested the relationship between occlusion location and baseline ischemic core, a known predictor of modified Rankin Scale (mRS) score at 90 days.

Methods: We analyzed a prospectively collected cohort of thrombolysis-eligible ischemic stroke patients from the International Stroke Perfusion Imaging Registry who underwent multimodal CT pretreatment. For the primary analysis, logistic regression was used to predict the effect of occlusion location and ischemic core on the likelihood of excellent (mRS 0-1) and favorable (mRS 0-2) 90-day outcomes.

Results: This study included 945 patients. The rates of excellent and favorable outcome in patients with distal occlusion (M2, M3 segment of middle cerebral artery, anterior cerebral artery, and posterior cerebral artery) were higher than M1 occlusions (mRS 0%-1%, 55% vs 37%; mRS 0%-2%, 73% vs 50%, < 0.001). Vessel occlusion location was not a strong predictor of outcomes compared to baseline ischemic core (area under the curve, mRS 0-1, 0.64 vs 0.83; mRS 0-2, 0.70 vs 0.86, < 0.001). There was no interaction between occlusion location and ischemic core (interaction coefficient 1.00, = 0.798).

Conclusions: Ischemic stroke patients with a distal occlusion have higher rate of excellent and favorable outcome than patients with an M1 occlusion. The baseline ischemic core was shown to be a more powerful predictor of functional outcome than the occlusion location, but the relationship between ischemic core and outcome does not different by occlusion locations.
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http://dx.doi.org/10.1212/WNL.0000000000007553DOI Listing
June 2019

Postpartum Period Is a Risk Factor for Cerebral Venous Thrombosis.

Stroke 2019 02;50(2):501-503

From the Department of Neurology (S.M.S., S.M.Z., J.M.C.), Academic Medical Center, Amsterdam, the Netherlands.

Background and Purpose- Pregnancy and the postpartum period are generally considered to be risk factors for cerebral venous thrombosis (CVT), but no controlled studies have quantified the risk. Methods- Case-control study using data of consecutive adult patients with CVT from 5 academic hospitals and controls from the Dutch MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). Men, women over the age of 50, women using oral contraceptives or with a recent abortion or miscarriage were excluded. We adjusted for age and history of cancer, and stratified for pregnancy versus postpartum, and 0 to 6 versus 7 to 12 weeks postpartum. Results- In total 163/813 cases and 1230/6296 controls were included. Cases were younger (median 38 versus 41 years) and more often had a history of cancer (14% versus 4%) than controls. In total 41/163 (25%) cases and 82/1230 (7%) controls were pregnant or postpartum (adjusted odds ratio, 3.8; 95% CI, 2.4-6.0). The association was fully attributable to an increased risk of CVT during the postpartum period (adjusted odds ratio, 10.6; 95% CI, 5.6-20.0). We found no association between pregnancy and CVT (adjusted odds ratio, 1.2; 95% CI, 0.6-2.3). The risk was highest during the first 6 weeks postpartum (adjusted odds ratio, 18.7; 95% CI, 8.3-41.9). Conclusions- Women who have recently delivered are at increased risk of developing CVT, while there does not seem to be an increased risk of CVT during pregnancy.
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http://dx.doi.org/10.1161/STROKEAHA.118.023017DOI Listing
February 2019

Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data.

Lancet Neurol 2018 10 18;17(10):895-904. Epub 2018 Sep 18.

Department of Neuroradiology, Pitié-Salpêtrière Hospital, Paris Hospitals Public Assistance, Paris, France.

Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion.

Methods: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered.

Findings: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69-2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0-4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94-16·49; p=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30-13·44, p=0·012).

Interpretation: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline.

Funding: Medtronic.
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October 2018

Intravenous Thrombolysis May Not Improve Clinical Outcome of Acute Ischemic Stroke Patients Without a Baseline Vessel Occlusion.

Front Neurol 2018 6;9:405. Epub 2018 Jun 6.

Department of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.

The benefit of thrombolysis in ischemic stroke patients without a visible vessel occlusion still requires investigation. This study tested the hypothesis that non-lacunar stroke patients with no visible vessel occlusion on baseline imaging would have a favorable outcome regardless of treatment with alteplase. We utilized a prospectively collected registry of ischemic stroke patients [the International Stroke Perfusion Imaging Registry (INSPIRE)] who had baseline computed tomographic perfusion and computed tomographic angiography. The rates of patients achieving modified Rankin Scale (mRS) 0-1 were compared between alteplase treated and untreated patients using logistic regression to generate odds ratios. Of 1569 patients in the INSPIRE registry, 1,277 were eligible for inclusion. Of these, 306 (24%) had no identifiable occlusion and were eligible for alteplase, with 141 (46%) of these patients receiving thrombolysis. The treated and untreated groups had significantly different median baseline National Institutes of Health Stroke Scale (NIHSS) [alteplase 8, interquartile range (IQR) 5-10, untreated 6, IQR 4-8, < 0.001] and median volume of baseline perfusion lesion [alteplase 5.6 mL, IQR 1.3-17.7 mL, untreated 2.6 mL, IQR 0-6.7 mL, < 0.001]. After propensity analysis, alteplase treated patients without a vessel occlusion were less likely to have an excellent outcome (mRS 0-1; 56%) than untreated (78.8%, OR, 0.42, 95% confidence interval, 0.24-0.75, = 0.003). In this non-randomized comparison, alteplase treatment in patients without an identifiable vessel occlusion did not result in higher rates of favorable outcome compared to untreated. However, treated patients displayed less favorable baseline prognostic factors than the untreated group. Further studies may be required to confirm this data.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997810PMC
June 2018

Excess stroke incidence in young Aboriginal people in South Australia: Pooled results from two population-based studies.

Int J Stroke 2018 10 16;13(8):811-814. Epub 2018 May 16.

2 Department of Neurology, Royal Adelaide Hospital, SA Health, Adelaide, South Australia, Australia.

Background Retrospective data indicate increased stroke incidence in Aboriginal/Torres Strait Islander (Indigenous) Australians, possibly with poorer outcomes. We present the first prospective population-based stroke incidence study in Indigenous Australians. Methods We pooled data from ASCEND and SEARCH, two prospective "ideal" South Australian stroke incidence studies, ASCEND conducted in urban Northwestern Adelaide (2009-2010) and SEARCH in five South Australian rural centers (2009-2011). We calculated age-standardized incidence for Aboriginal and non-Aboriginal people. Results The study population comprised 261,403 inhabitants. Among 432 first-ever strokes, 13 were in Aboriginal people (median age 51 vs. 78 years for non-Aboriginal people, p < 0.001). Age-standardized stroke incidence per 100,000 in Aboriginal patients (116, 95% CI: 95-137) was nearly two-fold that of non-Aboriginal patients (67, 95% CI: 51-84). Age-stratified excess incidence in Aboriginal people was restricted to those aged < 55 years (incidence rate ratio (IRR) 3.5, 95% CI: 2-7), particularly for intracerebral hemorrhage (IRR: 16, 95% CI: 4-61). Conclusion The excess stroke incidence in Aboriginal South Australians appears substantial, especially in those aged <55 years. Further work is required to delineate and address disparities.
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October 2018

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

N Engl J Med 2018 04;378(17):1573-1582

From the Departments of Medicine and Neurology, Melbourne Brain Centre (B.C.V.C., N.Y., B.Y., T.Y.W., D.G.S., E.R., H.Z., P.S., G.S., M.W.P., S.M.D.), and the Department of Radiology (P.J.M., R.J.D., S.J.B., P.M.D.), Royal Melbourne Hospital, and the Florey Institute of Neuroscience and Mental Health (L.C., N.Y., V.T., H.A., H.M., C.F.B., G.A.D.), University of Melbourne, Parkville, VIC, the Departments of Neurology (T.J.K.) and Radiology (R.S.), Royal Adelaide Hospital, and the Department of Neurology, Lyell McEwin Hospital (D.F.), Adelaide, SA, the Department of Neurosciences, Eastern Health and Eastern Health Clinical School (H.M.D., C.F.B.), and the Departments of Neurology (H.M., T.G.P.) and Radiology (W. Chong, R.V.C., L.-A.S.), Monash Medical Centre, Monash University, Clayton, VIC, the Departments of Neurology (V.T., M.S.) and Radiology (M.B., H.A.), Austin Hospital, Austin Health, Heidelberg, VIC, School of Medicine, Faculty of Health, Deakin University, Melbourne, VIC (H.A.), and the Departments of Medicine and Neurology, Melbourne Medical School, University of Melbourne and Western Health, Sunshine Hospital, St. Albans, VIC (T.W.), the Departments of Neurology (D.G.S., H.B.) and Radiology (K.R., D.L.), Princess Alexandra Hospital, and the Departments of Neurology (A.A.W., C.M.) and Radiology (A.C., K. Mitchell, J.C., K. Mahady), Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, the Departments of Neurology (P.B.) and Radiology (H.R., L.V.), Gold Coast University Hospital, Southport, QLD, and the Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, NSW (T.A., F.M., C.R.L., C.G.-E., M.W.P.), the Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney (M.K.), and the Department of Radiology, Royal North Shore Hospital (T.J.H., K.C.F., B.S.S.), St. Leonards, and the Department of Radiology, Westmead Hospital, Sydney (T.J.H., K.C.F., B.S.S.) - all in Australia; and the Departments of Neurology (T.Y.W., J.N.F.) and Radiology (W. Collecutt), Christchurch Hospital, Christchurch, New Zealand.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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 .).
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http://dx.doi.org/10.1056/NEJMoa1716405DOI Listing
April 2018

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost.

Front Neurol 2017 14;8:657. Epub 2017 Dec 14.

Gold Coast University Hospital, Southport, QLD, Australia.

Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.

Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014).

Results: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group ( = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years,  = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8),  = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5),  = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days,  = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days,  = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569,  = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365.

Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.

Clinical Trial Registration: http://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).
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http://dx.doi.org/10.3389/fneur.2017.00657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735082PMC
December 2017

Cerebral Venous Thrombosis in Older Patients.

Stroke 2018 01 4;49(1):197-200. Epub 2017 Dec 4.

From the Department of Neurology, Academic Medical Centre, Amsterdam, the Netherlands (S.M.Z., S.M.S, J.M.C.); Department of Neurology, Helsinki University Central Hospital, Finland (S.H., J.P., T.T); Department of Intensive Care, Royal Adelaide Hospital, South Australia, Australia (S.D.); Department of Neurology, Royal Adelaide, Lyell McEwin Hospitals (T.K.) and Department of Medicine (T.K.), University of Adelaide, South Australia, Australia; Department of Clinical Neuroscience/Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden (E.L., K.J., T.T); Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (E.L., K.J., T.T.); the Divisions of Neuroradiology (D.M.M.) and Neurology (F.L.S.), University Health Network and the University of Toronto, Canada.

Background And Purpose: Cerebral venous thrombosis (CVT) is rare in older patients. We investigated whether clinical features and outcomes differ in older and younger patients.

Methods: We used data from a multicenter observational registry of consecutive adult patients with CVT admitted between 1987 and 2016. We compared demographics, clinical manifestations, and outcomes between older (upper quartile of the age distribution) and younger (lower 3 quartiles of the age distribution) patients.

Results: Data for 843 patients with CVT were available. The median age was 43 years (interquartile range, 30-55 years). Older patients (≥55 years; n=222) were less often women than younger patients (48% versus 71%; <0.001) and less often reported headache (63% versus 87%; <0.001). Cancer was more common in older patients (24% versus 9%; <0.001), especially solid malignancies (19% versus 5%; <0.001). Outcome at follow-up was worse in older patients (modified Rankin Scale, 3-6; adjusted odds ratio, 2.68; 95% confidence interval, 1.78-4.03; mortality, adjusted odds ratio, 2.13; 95% confidence interval, 1.09-4.19).

Conclusions: The sex ratio of CVT is evenly distributed in older patients, probably because of the dissipation of hormonal influences. Malignancy should be considered as a potential precipitant in older patients with CVT.
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http://dx.doi.org/10.1161/STROKEAHA.117.019483DOI Listing
January 2018

Cerebral blood volume lesion extent predicts functional outcome in patients with vertebral and basilar artery occlusion.

Int J Stroke 2019 07 21;14(5):540-547. Epub 2017 Nov 21.

1 Department of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.

Background: CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed Tomography Angiography source images (CTA-SI) predicts functional outcome in patients with basilar artery occlusion.

Aims: We assessed the prognostic value of pc-ASPECTS on CT perfusion in patients with vertebral and basilar artery occlusion (VBAO) in comparison with CTA-SI.

Methods: Whole-brain CT perfusion from consecutive stroke patients with VBAO at four stroke centers was retrospectively analyzed. pc-ASPECTS - a 10-point score assessing hypoattenuation on CTA-SI - was calculated from CT perfusion parameters as focally reduced cerebral blood flow or cerebral blood volume, focally increased time to peak of the deconvolved tissue residue function (Tmax) or mean transit time. Two investigators independently reviewed the images. Reliability was assessed with intraclass correlation coefficient. Good outcome was defined as modified Rankin scale ≤3 at three months.

Results: We included 60 patients with VBAO. After assessment of four CT perfusion maps simultaneously, area-under-ROC curve (AROC) was 0.83 (95%CI 0.72-0.93) for cerebral blood volume, 0.76 (95%CI 0.64-0.89) for cerebral blood flow, 0.77 (95%CI 0.64-0.89) for Tmax, 0.70 (95%CI 0.56-0.84) for mean transit time versus area-under-ROC curve 0.64 (95%CI 0.50-0.79) for CTA-SI. Cerebral blood volume had greater accuracy compared with CTA-SI for poor outcome (p = 0.04). In logistic regression analysis, cerebral blood volume pc-ASPECTS≤8 was independently associated with poor outcome (OR 9.3 95%CI 2.2-41; p = 0.003, adjusted for age and clinical severity). Inter-rater agreement was substantial for cerebral blood volume pc-ASPECTS (intraclass correlation coefficient 0.82 95%CI 0.71-0.90 versus 0.67 for CTA-SI 95%CI 0.43-0.81).

Conclusions: Cerebral blood volume pc-ASPECTS may identify VBAO patients at higher risk of disability.
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http://dx.doi.org/10.1177/1747493017744465DOI Listing
July 2019

Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study.

Int J Stroke 2018 04 27;13(3):328-334. Epub 2017 Sep 27.

16 Royal Brisbane & Women's Hospital, University of Queensland, Brisbane, Queensland, Australia.

Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061.
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http://dx.doi.org/10.1177/1747493017733935DOI Listing
April 2018

Influence of Penumbral Reperfusion on Clinical Outcome Depends on Baseline Ischemic Core Volume.

Stroke 2017 10 8;48(10):2739-2745. Epub 2017 Sep 8.

From the Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (C.C., M.P., C.L., L.L., A.B.); Public Health Stream, Hunter Medical Research Institute, Newcastle, Australia (M.C., C.O.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (X.C., Q.D.); Department of Neurology, Second Affiliated Hospital of Zhejiang University, Hangzhou, China (M.L.); Department of Neurology, Royal Adelaide Hospital, Australia (T.K.); and Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (K.B.).

Background And Purpose: In alteplase-treated patients with acute ischemic stroke, we investigated the relationship between penumbral reperfusion at 24 hours and clinical outcomes, with and without adjustment for baseline ischemic core volume.

Methods: Data were collected from consecutive acute ischemic stroke patients with baseline and follow-up perfusion imaging presenting to hospital within 4.5 hours of symptom onset at 7 hospitals. Logistic regression models were used for predicting the effect of the reperfused penumbral volume on the dichotomized modified Rankin Scale (mRS) at 90 days and improvement of National Institutes of Health Stroke Scale at 24 hours, both adjusted for baseline ischemic core volume.

Results: This study included 1507 patients. Reperfused penumbral volume had moderate ability to predict 90-day mRS 0 to 1 (area under the curve, 0.77; , 0.28; <0.0001). However, after adjusting for baseline ischemic core volume, the reperfused penumbral volume was a strong predictor of good functional outcome (area under the curve, 0.946; , 0.55; <0.0001). For every 1% increase in penumbral reperfusion, the odds of achieving mRS 0 to 1 at day 90 increased by 7.4%. Improvement in acute 24-hour National Institutes of Health Stroke Scale was also significantly related to the degree of reperfused penumbra (, 0.31; P<0.0001). This association was again stronger after adjustment for baseline ischemic core volume (, 0.41; <0.0001). For each 1% of penumbra that was reperfused, the 24-hour National Institutes of Health Stroke Scale decreased by 0.069 compared with baseline.

Conclusions: In patients treated with alteplase, the extent of the penumbra that is reperfused is a powerful predictor of early and late clinical outcomes, particularly when baseline ischemic core is taken into account.
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http://dx.doi.org/10.1161/STROKEAHA.117.018587DOI Listing
October 2017

Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study.

Stroke 2016 05 17;47(5):1377-80. Epub 2016 Mar 17.

From the Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia (N.H.C., J.J., T.J.K.); Department of Neurology, Lyell McEwin Hospital, Adelaide, Australia (J.M.L., T.J.K.); and Department of Medicine, University of Adelaide, Adelaide, Australia (J.N., J.J., T.J.K.).

Background And Purpose: Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009-2010).

Methods: Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0-1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0-3 and presentation delay <5 hours).

Results: In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 [192-240] per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%-10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%-18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4-18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13-31) using the permissive algorithm.

Conclusions: In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria). In similar populations, the permissive criteria predict that ≤22 strokes per 100 000 person-years may be eligible for ET.
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http://dx.doi.org/10.1161/STROKEAHA.116.013165DOI Listing
May 2016