2024 |
Postol N, Barton J, Wakely L, Bivard A, Spratt NJ, Marquez J, '"Are we there yet?" expectations and experiences with lower limb robotic exoskeletons: a qualitative evaluation of the therapist perspective.', Disabil Rehabil, 46 1023-1030 (2024) [C1]
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Nova |
2024 |
Dos Santos A, Visser M, Lin L, Bivard A, Churilov L, Parsons MW, 'Novel artificial intelligence-based hypodensity detection tool improves clinician identification of hypodensity on non-contrast computed tomography in stroke patients', FRONTIERS IN NEUROLOGY, 15 (2024)
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2024 |
Werdiger F, Yogendrakumar V, Visser M, Kolacz J, Lam C, Hill M, et al., 'Clinical performance review for 3-D Deep Learning segmentation of stroke infarct from diffusion-weighted images', Neuroimage: Reports, 4 (2024) [C1]
Introduction: During the subacute phase of ischemic stroke, MR diffusion-weighted imaging (DWI) is used to assess the extent of tissue injury. Segmentation of DWI infarct is chall... [more]
Introduction: During the subacute phase of ischemic stroke, MR diffusion-weighted imaging (DWI) is used to assess the extent of tissue injury. Segmentation of DWI infarct is challenging due to disease variability, but Deep Learning (DL) provides a solution, outperforming existing methods on small datasets. However, a lack of clinically meaningful performance evaluation hinders clinical translation. Here we develop a DL DWI segmentation tool and provide clinical performance review. Methods: Subjects in this retrospective study presented with stroke symptoms and later underwent DWI imaging. DL architectures U-Net and DenseNet were used to develop a DWI segmentation tool. The Dice Similarly Coefficient (DSC) was used to select the best- and worst-performing model. Clinical experts reviewed these models on the clinical test set, agreeing with the model if no 'significant¿ error was present. The average agreement with the model and interrater agreement was also derived. Results: In total, 573 participants with an ischemic stroke were included. The DenseNet delivered the best model (DSC = 0.831 ± 0.064) with a mean inference time of 0.07 s. Clinicians compared this with the worst model (U-Net, DSC = 0.759 ± 0.122), agreeing with the DenseNet predictions more than the U-Net (83.8 % vs. 79.3 %). Clinicians also agreed with each other more over performance interpretation when evaluating the DenseNet over the U-Net (87.9 % vs. 72.7 %). Conclusion: Our DWI segmentation tool achieved high performance with clinical review providing meaningful performance evaluation. Model development will continue towards prospective deployment before which clinical review will be repeated. This work will benefit physicians in assessing patient prognosis.
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2023 |
Lim NE, Chia B, Bulsara MK, Parsons M, Hankey GJ, Bivard A, 'Automated CT Perfusion Detection of the Acute Infarct Core in Ischemic Stroke: A Systematic Review and Meta-Analysis', CEREBROVASCULAR DISEASES, 52 97-109 (2023) [C1]
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2023 |
Dunphy H, Garcia-Esperon C, Hong JB, Manoczki C, Wilson D, Chew BLA, et al., 'Endovascular thrombectomy for acute ischaemic stroke improves and maintains function in the very elderly: A multicentre propensity score matched analysis', EUROPEAN STROKE JOURNAL, 8 191-198 (2023) [C1]
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Nova |
2023 |
Garcia-Esperon C, Bivard A, Johns H, Chen C, Churilov L, Lin L, Butcher K, 'Association of Endovascular Thrombectomy With Functional Outcome in Patients With Acute Stroke With a Large Ischemic Core', NEUROLOGY, 100 (2023)
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2023 |
Yang J, Wu Y, Gao X, Shang Q, Xu Y, Han Q, et al., 'Poor collateral flow with severe hypoperfusion explains worse outcome in acute stroke patients with atrial fibrillation.', Int J Stroke, 18 689-696 (2023) [C1]
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Nova |
2023 |
Roaldsen MB, Eltoft A, Wilsgaard T, Christensen H, Engelter ST, Indredavik B, et al., 'Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial', The Lancet Neurology, 22 117-126 (2023) [C1]
Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended ... [more]
Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014¿000096¿80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9¿81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88¿1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74¿2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53¿8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67¿1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.
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2023 |
Wang P, Chen W, Chen C, Bivard A, Yu G, Parsons MW, Lin L, 'Association of Perfusion Lesion Variables With Functional Outcome in Patients With Mild Stroke and Large Vessel Occlusion Managed Medically.', Neurology, 100 e627-e638 (2023) [C1]
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Nova |
2023 |
Werdiger F, Gotla S, Visser M, Kolacz J, Yogendrakumar V, Beharry J, et al., 'Automated occlusion detection for the diagnosis of acute ischemic stroke: A detailed performance review.', Eur J Radiol, 164 110845 (2023) [C1]
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2023 |
Bivard A, Garcia-Esperon C, Churilov L, Spratt N, Russell M, Campbell BC, et al., 'Tenecteplase versus alteplase for stroke thrombolysis evaluation (TASTE): A multicentre, prospective, randomized, open-label, blinded-endpoint, controlled phase III non-inferiority trial protocol', INTERNATIONAL JOURNAL OF STROKE, 18 751-756 (2023)
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2023 |
Alamowitch S, Turc G, Palaiodimou L, Bivard A, Cameron A, De Marchis GM, et al., 'European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke', European Stroke Journal, 8 8-54 (2023) [C1]
Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischa... [more]
Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of <4.5 h duration who are eligible for IVT, tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS of <4.5 h duration who are eligible for IVT, we recommend against using tenecteplase at a dose of 0.40 mg/kg (low evidence, strong recommendation). For patients with AIS of <4.5 h duration with prehospital management with a mobile stroke unit who are eligible for IVT, we suggest tenecteplase 0.25 mg/kg over alteplase 0.90 mg/kg (low evidence, weak recommendation). For patients with large vessel occlusion (LVO) AIS of <4.5 h duration who are eligible for IVT, we recommend tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS on awakening from sleep or AIS of unknown onset who are selected with non-contrast CT, we recommend against IVT with tenecteplase 0.25 mg/kg (low evidence, strong recommendation). Expert consensus statements are also provided. Tenecteplase 0.25 mg/kg may be favoured over alteplase 0.9 mg/kg for patients with AIS of <4.5 h duration in view of comparable safety and efficacy data and easier administration. For patients with LVO AIS of <4.5 h duration who are IVT-eligible, IVT with tenecteplase 0.25 mg/kg is preferable over skipping IVT before MT, even in the setting of a direct admission to a thrombectomy-capable centre. IVT with tenecteplase 0.25 mg/kg may be a reasonable alternative to alteplase 0.9 mg/kg for patients with AIS on awakening from sleep or AIS of unknown onset and who are IVT-eligible after selection with advanced imaging.
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2023 |
Gyawali P, Lillicrap TP, Esperon CG, Bhattarai A, Bivard A, Spratt N, 'Whole Blood Viscosity and Cerebral Blood Flow in Acute Ischemic Stroke.', Semin Thromb Hemost, (2023) [C1]
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2023 |
Tomari S, Lillicrap T, Garcia-Esperon C, Kashida YT, Bivard A, Lin L, et al., 'Ischemic Lesion Growth in Patients with a Persistent Target Mismatch After Large Vessel Occlusion', Clinical Neuroradiology, 33 41-48 (2023) [C1]
Background: Failure to reperfuse a¿cerebral occlusion resulting in a¿persistent penumbral pattern has not been fully described. Methods: We retrospectively reviewed patients with ... [more]
Background: Failure to reperfuse a¿cerebral occlusion resulting in a¿persistent penumbral pattern has not been fully described. Methods: We retrospectively reviewed patients with anterior large vessel occlusion who did not receive reperfusion, and underwent repeated perfusion imaging, with baseline imaging <¿6¿h after onset and follow-up scans from 16¿168¿h. A¿persistent target mismatch (PTM) was defined as core volume of <¿100¿mL, mismatch ratio >¿1.2, and mismatch volume >¿10¿mL on follow-up imaging. Patients were divided into PTM or non-PTM groups. Ischemic core and penumbral volumes were compared between baseline and follow-up imaging between the two groups, and collateral flow status assessed using CT perfusion collateral index. Results: A total of 25 patients (14¿PTM and 11¿non-PTM) were enrolled in the study. Median core volumes increased slightly in the PTM group, from 22 to 36¿ml. There was a¿much greater increase in the non-PTM group, from 57 to 190¿ml. Penumbral volumes were stable in the PTM group from a¿median of 79¿ml at baseline to 88¿ml at follow-up, whereas penumbra was reduced in the non-PTM group, from 120 to 0¿ml. Collateral flow status was also better in the PTM group and the median collateral index was 33% compared with 44% in the non-PTM group (p¿= 0.043). Conclusion: Multiple patients were identified with limited core growth and large penumbra (persistent target mismatch) >¿16¿h after stroke onset, likely due to more favorable collateral flow.
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Nova |
2023 |
Werdiger F, Visser M, Bivard A, Li X, Gotla S, Sharobeam A, et al., 'Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV.', Neuroimage, 271 119985 (2023) [C1]
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2023 |
Werdiger F, Parsons MW, Visser M, Levi C, Spratt N, Kleinig T, et al., 'Machine learning segmentation of core and penumbra from acute stroke CT perfusion data', Frontiers in Neurology, 14 (2023) [C1]
Introduction: Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for tre... [more]
Introduction: Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for treatment through identification of reversible and irreversible tissue injury. Traditionally, this has been done via setting single perfusion thresholds on two or four CTP parameter maps. We present an alternative model for the estimation of tissue fate using multiple perfusion measures simultaneously. Methods: We used machine learning (ML) models based on four different algorithms, combining four CTP measures (cerebral blood flow, cerebral blood volume, mean transit time and delay time) plus 3D-neighborhood (patch) analysis to predict the acute ischemic core and perfusion lesion volumes. The model was developed using 86 patient images, and then tested further on 22 images. Results: XGBoost was the highest-performing algorithm. With standard threshold-based core and penumbra measures as the reference, the model demonstrated moderate agreement in segmenting core and penumbra on test images. Dice similarity coefficients for core and penumbra were 0.38 ± 0.26 and 0.50 ± 0.21, respectively, demonstrating moderate agreement. Skull-related image artefacts contributed to lower accuracy. Discussion: Further development may enable us to move beyond the current overly simplistic core and penumbra definitions using single thresholds where a single error or artefact may lead to substantial error.
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Nova |
2023 |
Sun J, Lam C, Christie L, Blair C, Li X, Werdiger F, et al., 'Risk factors of hemorrhagic transformation in acute ischaemic stroke: A systematic review and meta-analysis', Frontiers in Neurology, 14 (2023) [C1]
Background: Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis ai... [more]
Background: Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)]. Methods: Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated. Results: A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212¿5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041¿1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970¿7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060¿1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001¿1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565¿0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012¿1.866, I2 = 86.4%) were predictors of sICH after EVT. Conclusion: Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.
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2023 |
Majoie CB, Cavalcante F, Gralla J, Yang P, Kaesmacher J, Treurniet KM, et al., 'Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials', The Lancet, 402 965-974 (2023) [C1]
Background: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of en... [more]
Background: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. Methods: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms ¿stroke¿, ¿endovascular treatment¿, ¿intravenous thrombolysis¿, and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. Findings: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1¿5) for participants who received endovascular treatment alone and 2 (1¿4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76¿1·04). Any intracranial haemorrhage (0·82, 0·68¿0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. Interpretation: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. Funding: Stryker and Amsterdam University Medical Centers, University of Amsterdam.
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2023 |
Gao L, Tan E, Chen C, Kleinig T, Yan B, Cheung A, et al., 'Cost-Effectiveness of Endovascular Thrombectomy in M2 Occlusion Stroke: Real-World Experience Versus Clinical Trials', Journal of Endovascular Therapy, (2023) [C1]
Objectives: This study sought to establish the cost-effectiveness of endovascular thrombectomy (EVT) in M2 occlusions compared with patients who did not have EVT using both real-w... [more]
Objectives: This study sought to establish the cost-effectiveness of endovascular thrombectomy (EVT) in M2 occlusions compared with patients who did not have EVT using both real-world and clinical trial evidence. Methods: The effectiveness of EVT in M2 occlusions was informed by the International Stroke Perfusion Imaging Registry (INSPIRE, real-world data for a wide range of strokes) and HERMES collaboration, trial data. Patients who received EVT and non-EVT treatment from INSPIRE were matched according to baseline characteristics. A Markov model with 7 health states defined by the 3-month modified Rankin scale (mRS) was constructed. Endovascular thrombectomy and non-EVT-treated patients in real-world, and clinical trials were run through the Markov model separately to generate the results from a limited societal perspective. National statistics and published literature informed the long-term probability of recurrent stroke, mortality, costs of management post-stroke, non-medical care, and nursing home care. Results: A total of 83 (42 EVT and 41 non-EVT) patients were matched of 278 (45 EVT and 233 non-EVT) patients in INSPIRE who had M2 occlusion stroke at presentation. The long-term simulation estimated that offering EVT to M2 occlusion stroke patients was associated with greater benefits (5.48 EVT vs 5.24 non-EVT quality-adjusted life year [QALY]) and higher costs (A$133 457 EVT vs A$126 127 non-EVT) compared with non-EVT treatment in real-world from a limited societal perspective. The incremental cost-effectiveness ratio (ICER) of EVT in real-world was A$29 981 (¿19 488)/QALY. The analysis using the data from HERMES collaboration yielded consistent results for the EVT patients. Comparison with real-world cost-effectiveness analyses of EVT in internal carotid artery/middle cerebral artery-M1 (ICA/MCA-M1) occlusion suggested a potential reduced QALY gains and increased ICER in M2 occlusions. Conclusions: Our study suggested that the benefits gained from EVT in M2 occlusion stroke in the real-world were similar to that derived from the clinical trials. The clinical and cost benefits from EVT appeared to be reduced in M2 compared with that from the ICA/MCA-M1 occlusions. Clinical Impact: Our study has provided valuable insights into the clinical significance of endovascular therapy (EVT) in the context of M2 occlusion stroke within a real-world setting. It is noteworthy that our findings indicate that the benefits obtained from EVT in M2 occlusion stroke closely align with those observed in controlled clinical trials. However, it is essential to recognize that there is a reduction in the clinical and cost-related advantages when comparing M2 occlusions to more proximal ICA/MCA-M1 occlusions.
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2023 |
Lin L, Blair C, Fu J, Cordato D, Cappelen-Smith C, Cheung A, et al., 'Prior anticoagulation and bridging thrombolysis improve outcomes in patients with atrial fibrillation undergoing endovascular thrombectomy for anterior circulation stroke.', J Neurointerv Surg, 15 e433-e437 (2023) [C1]
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2023 |
Gao L, Moodie M, Levi C, Lin L, Cheng X, Kleinig T, et al., 'Modelling the Long-Term Health Outcome and Costs of Thrombectomy in Treating Stroke Patients with Large Ischaemic Core: Comparison between Clinical Trials and Real-World Data', CEREBROVASCULAR DISEASES, 52 137-144 (2023) [C1]
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Nova |
2023 |
Edwards LS, Cappelen-Smith C, Cordato D, Bivard A, Churilov L, Lin L, et al., 'Optimal CT perfusion thresholds for core and penumbra in acute posterior circulation infarction', Frontiers in Neurology, 14 (2023) [C1]
Background: At least 20% of strokes involve the posterior circulation (PC). Compared to the anterior circulation, posterior circulation infarction (POCI) are frequently misdiagnos... [more]
Background: At least 20% of strokes involve the posterior circulation (PC). Compared to the anterior circulation, posterior circulation infarction (POCI) are frequently misdiagnosed. CT perfusion (CTP) has advanced stroke care by improving diagnostic accuracy and expanding eligibility for acute therapies. Clinical decisions are predicated upon precise estimates of the ischaemic penumbra and infarct core. Current thresholds for defining core and penumbra are based upon studies of anterior circulation stroke. We aimed to define the optimal CTP thresholds for core and penumbra in POCI. Methods: Data were analyzed from 331-patients diagnosed with acute POCI enrolled in the International-stroke-perfusion-registry (INSPIRE). Thirty-nine patients with baseline multimodal-CT with occlusion of a large PC-artery and follow up diffusion weighted MRI at 24¿48 h were included. Patients were divided into two-groups based on artery-recanalization on follow-up imaging. Patients with no or complete recanalisation were used for penumbral and infarct-core analysis, respectively. A Receiver operating curve (ROC) analysis was used for voxel-based analysis. Optimality was defined as the CTP parameter and threshold which maximized the area-under-the-curve. Linear regression was used for volume based analysis determining the CTP threshold which resulted in the smallest mean volume difference between the acute perfusion lesion and follow up MRI. Subanalysis of PC-regions was performed. Results: Mean transit time (MTT) and delay time (DT) were the best CTP parameters to characterize ischaemic penumbra (AUC = 0.73). Optimal thresholds for penumbra were a DT >1 s and MTT>145%. Delay time (DT) best estimated the infarct core (AUC = 0.74). The optimal core threshold was a DT >1.5 s. The voxel-based analyses indicated CTP was most accurate in the calcarine (Penumbra-AUC = 0.75, Core-AUC = 0.79) and cerebellar regions (Penumbra-AUC = 0.65, Core-AUC = 0.79). For the volume-based analyses, MTT >160% demonstrated best correlation and smallest mean-volume difference between the penumbral estimate and follow-up MRI (R2 = 0.71). MTT >170% resulted in the smallest mean-volume difference between the core estimate and follow-up MRI, but with poor correlation (R2 = 0.11). Conclusion: CTP has promising diagnostic utility in POCI. Accuracy of CTP varies by brain region. Optimal thresholds to define penumbra were DT >1 s and MTT >145%. The optimal threshold for core was a DT >1.5 s. However, CTP core volume estimates should be interpreted with caution.
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Nova |
2023 |
Tsivgoulis G, Katsanos AH, Sandset EC, Turc G, Nguyen TN, Bivard A, et al., 'Thrombolysis for acute ischaemic stroke: current status and future perspectives', The Lancet Neurology, 22 418-429 (2023) [C1]
Alteplase is currently the only approved thrombolytic agent for treatment of acute ischaemic stroke, but interest is burgeoning in the development of new thrombolytic agents for s... [more]
Alteplase is currently the only approved thrombolytic agent for treatment of acute ischaemic stroke, but interest is burgeoning in the development of new thrombolytic agents for systemic reperfusion with an improved safety profile, increased efficacy, and convenient delivery. Tenecteplase has emerged as a potential alternative thrombolytic agent that might be preferred over alteplase because of its ease of administration and reported efficacy in patients with large vessel occlusion. Ongoing research efforts are also looking at potential improvements in recanalisation with the use of adjunct therapies to intravenous thrombolysis. New treatment strategies are also emerging that aim to reduce the risk of vessel reocclusion after intravenous thrombolysis administration. Other research endeavors are looking at the use of intra-arterial thrombolysis after mechanical thrombectomy to induce tissue reperfusion. The growing implementation of mobile stroke units and advanced neuroimaging could boost the number of patients who can receive intravenous thrombolysis by shortening onset-to-treatment times and identifying patients with salvageable penumbra. Continued improvements in this area will be essential to facilitate the ongoing research endeavors and to improve delivery of new interventions.
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2023 |
Gao L, Parsons M, Churilov L, Zhao H, Campbell BCV, Yan B, et al., 'Cost-effectiveness of tenecteplase versus alteplase for stroke thrombolysis evaluation trial in the ambulance', European Stroke Journal, 8 448-455 (2023) [C1]
Background: Tenecteplase administered to patients with ischaemic stroke in a mobile stroke unit (MSU) has been shown to reduce the perfusion lesion volumes and result in ultra-ear... [more]
Background: Tenecteplase administered to patients with ischaemic stroke in a mobile stroke unit (MSU) has been shown to reduce the perfusion lesion volumes and result in ultra-early recovery. We now seek to assess the cost-effectiveness of tenecteplase in the MSU. Methods: A within-trial (TASTE-A) economic analysis and a model-based long-term cost-effectiveness analysis were performed. This post hoc within-trial economic analysis utilised the patient-level data (intention to treat, ITT) prospectively collected over the trial to calculate the difference in both healthcare costs and quality-adjusted life years (QALYs, estimated from modified Rankin scale score). A Markov microsimulation model was developed to simulate the long-term costs and benefits. Results: In total, there were 104 patients with ischaemic stroke randomised to tenecteplase (n = 55) or alteplase (n = 49) treatment groups, respectively in the TASTE-A trial. The ITT-based analysis showed that treatment with tenecteplase was associated with non-signficantly lower costs (A$28,903 vs A$40,150 (p = 0.056)) and greater benefits (0.171 vs 0.158 (p = 0.457)) than that for the alteplase group over the first 90 days post the index stroke. The long-term model showed that tenecteplase led to greater savings in costs (-A$18,610) and more health benefits (0.47 QALY or 0.31 LY gains). Tenecteplase-treated patients had reduced costs for rehospitalisation (-A$1464), nursing home care (-A$16,767) and nonmedical care (-A$620) per patient. Conclusions: Treatment of ischaemic stroke patients with tenecteplase appeared to be cost-effective and improve QALYs in the MSU setting based on Phase II data. The reduced total cost from tenecteplase was driven by savings from acute hospitalisation and reduce need for nursing home care.
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2023 |
Lin L, Zhang H, Liu F, Chen C, Chen C, Bivard A, et al., 'Bridging Thrombolysis Before Endovascular Therapy in Stroke Patients With Faster Core Growth.', Neurology, 100 e2083-e2092 (2023) [C1]
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Nova |
2022 |
Coote S, Mackey E, Alexandrov AW, Cadilhac DA, Alexandrov AV, Easton D, et al., 'The Mobile Stroke Unit Nurse: An International Exploration of Their Scope of Practice, Education, and Training.', J Neurosci Nurs, 54 61-67 (2022) [C1]
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2022 |
Tan Z, Parsons M, Bivard A, Sharma G, Mitchell P, Dowling R, et al., 'Comparison of Computed Tomography Perfusion and Multiphase Computed Tomography Angiogram in Predicting Clinical Outcomes in Endovascular Thrombectomy', STROKE, 53 2926-2934 (2022) [C1]
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2022 |
Valente M, Bivard A, Cheung A, Manning NW, Parsons MW, 'CT vascular territory mapping: a novel method to identify large vessel occlusion collateral', NEURORADIOLOGY, 65 113-119 (2022) [C1]
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2022 |
Churilov L, Bivard A, Parsons MW, 'Tenecteplase versus alteplase for early treatment of ischaemic stroke Reply', LANCET NEUROLOGY, 21 959-959 (2022)
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2022 |
Sarraj A, Parsons M, Bivard A, Hassan AE, Abraham MG, Wu T, et al., 'Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies.', Ann Neurol, 91 629-639 (2022) [C1]
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Nova |
2022 |
Mitchell PJ, Yan B, Churilov L, Dowling RJ, Bush SJ, Bivard A, et al., 'Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial', The Lancet, 400 116-125 (2022) [C1]
Background: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusi... [more]
Background: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). Methods: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0¿2 or return to baseline at 90 days, with a non-inferiority margin of ¿0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. Findings: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference ¿0·051, two-sided 95% CI ¿0·160 to 0·059; per-protocol risk difference ¿0·062, two-sided 95% CI ¿0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22¿13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46¿1·84). Interpretation: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. Funding: Australian National Health and Medical Research Council and Stryker USA.
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2022 |
Bivard A, Churilov L, Ma H, Levi C, Campbell B, Yassi N, et al., 'Does variability in automated perfusion software outputs for acute ischemic stroke matter? Reanalysis of EXTEND perfusion imaging', CNS NEUROSCIENCE & THERAPEUTICS, 28 139-144 (2022) [C1]
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Nova |
2022 |
Bivard A, Zhao H, Coote S, Campbell B, Churilov L, Yassi N, et al., 'Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit', BMJ OPEN, 12 (2022)
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2022 |
Bivard A, Zhao H, Churilov L, Campbell BCV, Coote S, Yassi N, et al., 'Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomised, open-label trial', The Lancet Neurology, 21 520-527 (2022) [C1]
Background: Mobile stroke units (MSUs) equipped with a CT scanner reduce time to thrombolytic treatment and improve patient outcomes. We tested the hypothesis that tenecteplase ad... [more]
Background: Mobile stroke units (MSUs) equipped with a CT scanner reduce time to thrombolytic treatment and improve patient outcomes. We tested the hypothesis that tenecteplase administered in an MSU would result in superior reperfusion at hospital arrival, when compared with alteplase. Methods: The TASTE-A trial is a phase 2, randomised, open-label trial at the Melbourne MSU and five tertiary hospitals in Melbourne, VIC, Australia. Patients (aged =18 years) with ischaemic stroke who were eligible for thrombolytic treatment were randomly allocated in the MSU to receive, within 4·5 h of symptom onset, either standard-of-care alteplase (0·9 mg/kg [maximum 90 mg], administered intravenously with 10% as a bolus over 1 min and 90% as an infusion over 1 h), or the investigational product tenecteplase (0·25 mg/kg [maximum 25 mg], administered as an intravenous bolus over 10 s), before being transported to hospital for ongoing care. The primary outcome was the volume of the perfusion lesion on arrival at hospital, assessed by CT-perfusion imaging. Secondary safety outcomes were modified Rankin Scale (mRS) score of 5 or 6 at 90 days, symptomatic intracerebral haemorrhage and any haemorrhage within 36 h, and death at 90 days. Assessors were masked to treatment allocation. Analysis was by intention-to-treat. The trial was registered with ClinicalTrials.gov, NCT04071613, and is completed. Findings: Between June 20, 2019, and Nov 16, 2021, 104 patients were enrolled and randomly allocated to receive either tenecteplase (n=55) or alteplase (n=49). The median age of patients was 73 years (IQR 61¿83), and the median NIHSS at baseline was 8 (5¿14). On arrival at the hospital, the perfusion lesion volume was significantly smaller with tenecteplase (median 12 mL [IQR 3¿28]) than with alteplase (35 mL [18¿76]; adjusted incidence rate ratio 0·55, 95% CI 0·37¿0·81; p=0·0030). At 90 days, an mRS of 5 or 6 was reported in eight (15%) patients allocated to tenecteplase and ten (20%) patients allocated to alteplase (adjusted odds ratio [aOR] 0·70, 95% CI 0·23¿2·16; p=0·54). Five (9%) patients allocated to tenecteplase and five (10%) patients allocated to alteplase died from any cause at 90 days (aOR 1·12, 95% CI 0·26¿4·90; p=0·88). No cases of symptomatic intracerebral haemorrhage were reported within 36 h with either treatment. Up to day 90, 13 serious adverse events were noted: five (5%) in patients treated with tenecteplase, and eight (8%) in patients treated with alteplase. Interpretation: Treatment with tenecteplase on the MSU in Melbourne resulted in a superior rate of early reperfusion compared with alteplase, and no safety concerns were noted. This trial provides evidence to support the use of tenecteplase and MSUs in an optimal model of stroke care. Funding: Melbourne Academic Centre for Health.
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2022 |
Garcia-Esperon C, Bivard A, Johns H, Chen C, Churilov L, Lin L, et al., 'Association of Endovascular Thrombectomy With Functional Outcome in Patients With Acute Stroke With a Large Ischemic Core.', Neurology, 99 e1345-e1355 (2022) [C1]
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Nova |
2022 |
Gyawali P, Lillicrap TP, Tomari S, Bivard A, Holliday E, Parsons M, et al., 'Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke', Neurological Sciences, 43 2375-2381 (2022) [C1]
Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk... [more]
Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2¿h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.
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Nova |
2022 |
Ryan A, Paul CL, Cox M, Whalen O, Bivard A, Attia J, et al., 'TACTICS-Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship: evaluating the effectiveness of an 'implementation intervention' in providing better patient access to reperfusion therapies: protocol for a non-randomised controlled stepped wedge cluster trial in acute stroke', BMJ OPEN, 12 (2022)
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2022 |
Kwok JS, Fox K, Bil C, Langenberg F, Balabanski AH, Dos Santos A, et al., 'Bringing CT Scanners to the Skies: Design of a CT Scanner for an Air Mobile Stroke Unit', Applied Sciences (Switzerland), 12 (2022) [C1]
Stroke is the second most common cause of death and remains a persistent health challenge globally. Due to its highly time-sensitive nature, earlier stroke treatments should be en... [more]
Stroke is the second most common cause of death and remains a persistent health challenge globally. Due to its highly time-sensitive nature, earlier stroke treatments should be enforced for improved patient outcome. The mobile stroke unit (MSU) was conceptualized and implemented to deliver the diagnosis and treatment to a stroke patient in the ultra-early time window (<1 h) in the pre-hospital setting and has shown to be clinically effective. However, due to geographical challenges, most rural communities are still unable to receive timely stroke intervention, as access to specialized stroke facilities for optimal stroke treatment poses a challenge. Therefore, the aircraft counterpart (Air-MSU) of the conventional road MSU offers a plausible solution to this shortcoming by expanding the catchment area for regional locations in Australia. The implementation of Air-MSU is currently hindered by several technical limitations, where current commercially available CT scanners are still oversized and too heavy to be integrated into a conventional helicopter emergency medical service (HEMS). In collaboration with the Australian Stroke Alliance and Melbourne Brain Centre, this article aims to explore the possibilities and methodologies in reducing the weight and, effectively, the size of an existing CT scanner, such that it can be retrofitted into the proposed search and rescue helicopter¿Agusta Westland AW189. The result will be Australia¿s first-ever customized CT scanner structure designed to fit in a search-and-rescue helicopter used for Air-MSU.
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Nova |
2021 |
Ermine CM, Bivard A, Parsons MW, Jean-Claude Baron, 'The ischemic penumbra: From concept to reality', International Journal of Stroke, 16 497-509 (2021) [C1]
The discovery that brain tissue could potentially be salvaged from ischaemia due to stroke, has led to major advances in the development of therapies for ischemic stroke. In this ... [more]
The discovery that brain tissue could potentially be salvaged from ischaemia due to stroke, has led to major advances in the development of therapies for ischemic stroke. In this review, we detail the advances in the understanding of this area termed the ischaemic penumbra, from its discovery to the evolution of imaging techniques, and finally some of the treatments developed. Evolving from animal studies from the 70s and 80s and translated to clinical practice, the field of ischemic reperfusion therapy has largely been guided by an array of imaging techniques developed to positively identify the ischemic penumbra, including positron emission tomography, computed tomography and magnetic resonance imaging. More recently, numerous penumbral identification imaging studies have allowed for a better understanding of the progression of the ischaemic core at the expense of the penumbra, and identification of patients than can benefit from reperfusion therapies in the acute phase. Importantly, 40 years of critical imaging research on the ischaemic penumbra have allowed for considerable extension of the treatment time window and better patient selection for reperfusion therapy. The translation of the penumbra concept into routine clinical practice has shown that ¿tissue is at least as important as time.¿
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2021 |
Nicolas K, Goodin P, Visser MM, Michie PT, Bivard A, Levi C, et al., 'Altered Functional Connectivity and Cognition Persists 4 Years After a Transient Ischemic Attack or Minor Stroke', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Garcia-Esperon C, Visser M, Churilov L, Miteff F, Bivard A, Lillicrap T, et al., 'Role of Computed Tomography Perfusion in Identification of Acute Lacunar Stroke Syndromes', STROKE, 52 339-343 (2021) [C1]
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Nova |
2021 |
Lin L, Zhang H, Chen C, Bivard A, Butcher K, Garcia-Esperon C, et al., 'Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy', STROKE, 52 3998-4006 (2021) [C1]
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Nova |
2021 |
Kashida YT, Garcia-Esperon C, Lillicrap T, Miteff F, Garcia-Bermejo P, Gangadharan S, et al., 'The Need for Structured Strategies to Improve Stroke Care in a Rural Telestroke Network in Northern New South Wales, Australia: An Observational Study', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Gao L, Bivard A, Parsons M, Spratt NJ, Levi C, Butcher K, et al., 'Real-World Cost-Effectiveness of Late Time Window Thrombectomy for Patients With Ischemic Stroke', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Postol N, Spratt NJ, Bivard A, Marquez J, 'Physiotherapy using a free-standing robotic exoskeleton for patients with spinal cord injury: a feasibility study', JOURNAL OF NEUROENGINEERING AND REHABILITATION, 18 (2021) [C1]
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Nova |
2021 |
Postol N, Grissell J, McHugh C, Bivard A, Spratt NJ, Marquez J, 'Effects of therapy with a free-standing robotic exoskeleton on motor function and other health indicators in people with severe mobility impairment due to chronic stroke: A quasi-controlled study.', Journal of Rehabilitation and Assistive Technologies Engineering, 8 1-13 (2021) [C1]
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Nova |
2021 |
Lin L, Yang J, Chen C, Tian H, Bivard A, Spratt NJ, et al., 'Association of Collateral Status and Ischemic Core Growth in Patients With Acute Ischemic Stroke', NEUROLOGY, 96 E161-E170 (2021) [C1]
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Nova |
2021 |
Edwards LS, Cappelen-Smith C, Cordato D, Bivard A, Churilov L, Parsons MW, 'Review of CT perfusion and current applications in posterior circulation stroke', Vessel Plus, 5 (2021) [C1]
Acute ischemic stroke is a leading cause of death and disability. Treatment efficacy is highly time-dependent. Approximately 20% of acute ischaemic stroke occurs in the posterior ... [more]
Acute ischemic stroke is a leading cause of death and disability. Treatment efficacy is highly time-dependent. Approximately 20% of acute ischaemic stroke occurs in the posterior circulation. Clinical presentation of posterior circulation stroke is subtle. Diagnosis is often delayed and frequently missed. CT perfusion has improved diagnostic accuracy and been integral to guiding acute therapy in patients with anterior circulation stroke. There are limited studies assessing the role of CT perfusion in posterior circulation stroke. This review provides a reference for interpretation of CT perfusion and summarises current evidence relating to applications in acute posterior circulation stroke.
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2021 |
Chen C, Parsons MW, Levi CR, Spratt NJ, Lin L, Kleinig T, et al., 'What Is the Optimal Target Mismatch Criteria for Acute Ischemic Stroke?', Frontiers in Neurology, 11 (2021) [C1]
We aimed to compare Perfusion Imaging Mismatch (PIM) and Clinical Core Mismatch (CCM) criteria in ischemic stroke patients to identify the effect of these criteria on selected pat... [more]
We aimed to compare Perfusion Imaging Mismatch (PIM) and Clinical Core Mismatch (CCM) criteria in ischemic stroke patients to identify the effect of these criteria on selected patient population characteristics and clinical outcomes. Patients from the INternational Stroke Perfusion Imaging REgistry (INSPIRE) who received reperfusion therapy, had pre-treatment multimodal CT, 24-h imaging, and 3 month outcomes were analyzed. Patients were divided into 3 cohorts: endovascular thrombectomy (EVT), intravenous thrombolysis alone with large vessel occlusion (IVT-LVO), and intravenous thrombolysis alone without LVO (IVT-nonLVO). Patients were classified using 6 separate mismatch criteria: PIM-using 3 different measures to define the perfusion deficit (Delay Time, Tmax, or Mean Transit Time); or CCM-mismatch between age-adjusted National Institutes of Health Stroke Scale and CT Perfusion core, defined as relative cerebral blood flow <30% within the perfusion deficit defined in three ways (as above). We assessed the eligibility rate for each mismatch criterion and its ability to identify patients likely to respond to treatment. There were 994 patients eligible for this study. PIM with delay time (PIM-DT) had the highest inclusion rate for both EVT (82.7%) and IVT-LVO (79.5%) cohorts. In PIM positive patients who received EVT, recanalization was strongly associated with achieving an excellent outcome at 90-days (e.g., PIM-DT: mRS 0-1, adjusted OR 4.27, P = 0.005), whereas there was no such association between reperfusion and an excellent outcome with any of the CCM criteria (all p > 0.05). Notably, in IVT-LVO cohort, 58.2% of the PIM-DT positive patients achieved an excellent outcome compared with 31.0% in non-mismatch patients following successful recanalization (P = 0.006). Conclusion: PIM-DT was the optimal mismatch criterion in large vessel occlusion patients, combining a high eligibility rate with better clinical response to reperfusion. No mismatch criterion was useful to identify patients who are most likely response to reperfusion in non-large vessel occlusion patients.
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Nova |
2021 |
Lim JC, Churilov L, Bivard A, Ma H, Dowling RJ, Campbell BC, et al., 'Does Intravenous Thrombolysis Within 4.5 to 9 Hours Increase Clot Migration Leading to Endovascular Inaccessibility?', STROKE, 52 1083-1086 (2021) [C1]
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2021 |
Bivard A, Levi C, Lin L, Cheng X, Aviv R, Spratt NJ, et al., 'Assessing the Relative Value of CT Perfusion Compared to Non-contrast CT and CT Angiography in Prognosticating Reperfusion-Eligible Acute Ischemic Stroke Patients', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Tan Z, Parsons M, Bivard A, Sharma G, Mitchell P, Dowling R, et al., 'Optimal Tissue Reperfusion Estimation by Computed Tomography Perfusion Post-Thrombectomy in Acute Ischemic Stroke', STROKE, 52 E760-E763 (2021) [C1]
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2021 |
Tran L, Lin L, Spratt N, Bivard A, Chew BLA, Evans JW, et al., 'Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Campbell BCV, Ma H, Parsons MW, Churilov L, Yassi N, Kleinig TJ, et al., '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 NEUROLOGY, 78 236-240 (2021) [C1]
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Nova |
2021 |
Gunasekera L, Churilov L, Mitchell P, Bivard A, Sharma G, Parsons MW, Yan B, 'Automated estimation of ischemic core prior to thrombectomy: comparison of two current algorithms', Neuroradiology, 63 1645-1649 (2021) [C1]
Purpose: Endovascular thrombectomy (EVT) improves clinical outcomes in ischemic stroke with large vessel occlusion. Clinical benefits are inversely proportional to size of the pre... [more]
Purpose: Endovascular thrombectomy (EVT) improves clinical outcomes in ischemic stroke with large vessel occlusion. Clinical benefits are inversely proportional to size of the pre-treatment ischemic core. This study compared estimated ischemic core volumes by two different CT perfusion (CTP) automated algorithms to the gold standard follow-up infarct volume using diffusion-weighted imaging (DWI) to assess for congruence, and thus eligibility for EVT. Methods: Retrospective, single-center cohort study of 102 patients presenting to a comprehensive stroke center between 2012 and 2018. Inclusion criteria were CT perfusion prior to EVT, successful EVT with mTIBI 2b-3 reperfusion, and DWI post-EVT. CTP data were retrospectively processed by two algorithms: ¿delay and dispersion insensitive deconvolution¿ (DISD, RAPID software) versus ¿delay and dispersion corrected single value decomposition¿ (ddSVD, Mistar software), using commercially available software. Core volumes were compared to follow up DWI using independent software (MRIcron). Agreement between each algorithm and DWI was estimated using Lin¿s concordance coefficient and analyzed using reduced major axis regression. Results: We included 102 patients. Both algorithms had excellent agreement with DWI (Lin¿s concordance coefficients: DISD 0.8 (95% CI: 0.73; 0.87), ddSVD 0.92 (95% CI: 0.89; 0.95). Compared to ddSVD (reduced major axis slope = 0.95), DISD exhibited a larger extent of proportional bias (slope = 1.12). Conclusion: The ddSVD algorithm better correlates with DWI follow-up infarct volume than DISD processing. The DISD algorithm overestimated larger ischemic cores which may lead to patient exclusion from thrombectomy based on selection by core volume.
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2020 |
Lin L, Chen C, Tian H, Bivard A, Spratt N, Levi CR, Parsons MW, 'Perfusion Computed Tomography Accurately Quantifies Collateral Flow After Acute Ischemic Stroke', STROKE, 51 1006-1009 (2020) [C1]
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Nova |
2020 |
Ostman C, Garcia-Esperon C, Lillicrap T, Tomari S, Holliday E, Levi C, et al., 'Multimodal Computed Tomography Increases the Detection of Posterior Fossa Strokes Compared to Brain Non-contrast Computed Tomography', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Lillicrap T, Pinheiro A, Miteff F, Garcia-Bermejo P, Gangadharan S, Wellings T, et al., 'No Evidence of the "Weekend Effect" in the Northern New South Wales Telestroke Network', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Hasnain MG, Paul CL, Attia JR, Ryan A, Kerr E, Oldmeadow C, et al., 'Thrombolysis implementation intervention and clinical outcome: A secondary analysis of a cluster randomized trial', BMC Cardiovascular Disorders, 20 432-440 (2020) [C1]
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Nova |
2020 |
Yang J, Wu Y, Gao X, Bivard A, Levi CR, Parsons MW, Lin L, 'Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke', STROKE, 51 2925-2933 (2020) [C1]
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Nova |
2020 |
Gangadharan S, Lillicrap T, Miteff F, Garcia-Bermejo P, Wellings T, O'Brien B, et al., 'Air vs. Road Decision for Endovascular Clot Retrieval in a Rural Telestroke Network', Frontiers in Neurology, 11 1-6 (2020) [C1]
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Nova |
2020 |
Bajorek B, Gao L, Lillicrap T, Bivard A, Garcia-Esperon C, Parsons M, et al., 'Exploring the Economic Benefits of Modafinil for Post-Stroke Fatigue in Australia: A Cost-Effectiveness Evaluation', Journal of Stroke and Cerebrovascular Diseases, 29 (2020) [C1]
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Nova |
2020 |
Gao L, Tan E, Moodie M, Parsons M, Spratt NJ, Levi C, et al., 'Reduced Impact of Endovascular Thrombectomy on Disability in Real-World Practice, Relative to Randomized Controlled Trial Evidence in Australia', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Bivard A, Huang X, Levi CR, Campbell BCV, Cheripelli BK, Chen C, et al., 'Comparing mismatch strategies for patients being considered for ischemic stroke tenecteplase trials', International Journal of Stroke, 15 507-515 (2020) [C1]
Background: Currently there are multiple variations of imaging-based patient selection mismatch methods in ischemic stroke. In the present study, we sought to compare the two most... [more]
Background: Currently there are multiple variations of imaging-based patient selection mismatch methods in ischemic stroke. In the present study, we sought to compare the two most common mismatch methods and identify if there were different effects on the outcome of a randomized clinical trial depending on the mismatch method used. Aims: Investigate the effect of clinical and imaging-based mismatch criteria on patient outcomes of a pooled cohort from randomized trials of intravenous tenecteplase versus alteplase. Methods: Baseline clinical and imaging scores were used to categorize patients as meeting either the DAWN mismatch (baseline NIHSS = 10, and age cut-offs for ischemic core volume) or DEFUSE 2 mismatch criteria (mismatch volume > 15 mL, mismatch ratio > 1.8 and ischemic core < 70 mL). We then investigated whether tenecteplase-treated patients had favorable odds of less disability (on modified Rankin scale, mRS) compared to those treated with alteplase, for clinical and imaging mismatch, respectively. Results: From 146 pooled patients, 71 received alteplase and 75 received tenecteplase. The overall pooled group did not show improved patient outcomes when treated with tenecteplase (mRS 0-1 OR 1.77, 95% CI 0.89¿3.51, p = 0.102) compared with alteplase. A total of 39 (27%) patients met both clinical and imaging mismatch criteria, 25 (17%) patients met only imaging criteria, 36 (25%) met only clinical mismatch criteria and, finally, 46 (31%) did not meet either of imaging or mismatch criteria. Patients treated with tenecteplase had more favorable outcomes when they met either imaging mismatch (mRS 0¿1, OR 2.33, 95% CI 1.13¿5.94, p = 0.032) or clinical mismatch criteria (mRS 0¿1, OR 2.15, 95% CI 1.142, 8.732, p = 0.027) but with differing proportions. Conclusion: Target mismatch selection was more inclusive and exhibited in a larger treatment effect between tenecteplase and alteplase.
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Nova |
2020 |
Nicolas K, Levi C, Evans TJ, Michie PT, Magin P, Quain D, et al., 'Cognition in the First Year After a Minor Stroke, Transient Ischemic Attack, or Mimic Event and the Role of Vascular Risk Factors', Frontiers in Neurology, 11 (2020) [C1]
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Nova |
2020 |
Bivard A, Churilov L, Parsons M, 'Artificial intelligence for decision support in acute stroke - current roles and potential', NATURE REVIEWS NEUROLOGY, 16 575-585 (2020)
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2020 |
Holliday E, Lillicrap T, Kleinig T, Choi PMC, Maguire J, Bivard A, et al., 'Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study', BMJ OPEN, 10 (2020)
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2020 |
Ng F, Venkatraman V, Parsons M, Bivard A, Sharma G, Churilov L, et al., 'Gradient of Tissue Injury after Stroke: Rethinking the Infarct versus Noninfarcted Dichotomy', Cerebrovascular Diseases, 49 32-38 (2020) [C1]
Aim: To evaluate the degree of variability in microstructural injury within and adjacent to regions identified as infarcted tissue using diffusion tensor imaging (DTI). Methods: I... [more]
Aim: To evaluate the degree of variability in microstructural injury within and adjacent to regions identified as infarcted tissue using diffusion tensor imaging (DTI). Methods: In this prospective longitudinal study, 18 patients presenting within 12 h of anterior circulation acute ischemic stroke who underwent CT perfusion (CTP) at baseline followed by fluid-attenuated inversion recovery (FLAIR) and DTI 1-month were analyzed. Four regions of interest (ROI) corresponding to the severity of hypoperfusion on CTP within and beyond the radiological infarct lesion defined on FLAIR were segmented. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified for each ROI and compared to a mirror homologue in the contralateral hemisphere. Ipsilateral to contralateral FA and MD ratios were compared across ROIs. Results: Lower FA and higher MD values were observed within both the infarct lesion and the peri-infarct tissue compared with their homologous contralateral brain regions (all comparisons p = 0.01). No difference was observed in FA and MD between remote nonhypoperfused tissue and its contralateral homologous region (FA p = 0.42, MD p = 0.99). The magnitude of asymmetry (ipsilateral/contralateral ratios) of FA and MD was greater with increasing severity of hypoperfusion in a dose-response pattern. Asymmetry greatest in the area of infarction with severe hypoperfusion, followed by infarction with moderate hypoperfusion, the peri-infarct hypoperfused tissue, and lastly the remote nonhypoperfused normal tissue (median on clustered quantile regression p = 0.01). Conclusion: A gradient of microstructural injury corresponding to the severity of ischemic insult is present within and beyond conventionally defined infarct boundaries. The traditional dichotomized notion of infarcted versus noninfarcted tissue widely adopted in clinical research and in practice warrants reexamination.
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2020 |
Thomalla G, Boutitie F, Ma H, Koga M, Ringleb P, Schwamm LH, et al., 'Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data', The Lancet, 396 1574-1584 (2020) [C1]
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 ... [more]
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 (I2=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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Nova |
2020 |
Postol N, Lamond S, Galloway M, Palazzi K, Bivard A, Spratt NJ, Marquez J, 'The Metabolic Cost of Exercising with a Robotic Exoskeleton: A Comparison of Healthy and Neurologically Impaired People', IEEE Transactions on Neural Systems and Rehabilitation Engineering, 28 3031-3039 (2020) [C1]
While neuro-recovery is maximized through active engagement, it has been suggested that the use of robotic exoskeletons in neuro-rehabilitation provides passive therapy. Using oxy... [more]
While neuro-recovery is maximized through active engagement, it has been suggested that the use of robotic exoskeletons in neuro-rehabilitation provides passive therapy. Using oxygen consumption (VO2) as an indicator of energy expenditure, we investigated the metabolic requirements of completing exercises in a free-standing robotic exoskeleton, with 20 healthy and 12 neurologically impaired participants (six with stroke, and six with multiple sclerosis (MS)). Neurological participants were evaluated pre- and post- 12 weeks of twice weekly robotic therapy. Healthy participants were evaluated in, and out of, the exoskeleton. Both groups increased their VO2 level from baseline during exoskeleton-assisted exercise (Healthy: mean change in VO2 = 2.10 ± 1.61 ml/kg/min, p =< 0.001; Neurological: 1.38 ± 1.22, p = 0.002), with a lower predicted mean in the neurological sample (-1.08, 95%CI -2.02, -0.14, p = 0.02). Healthy participants exercised harder out of the exoskeleton than in it (difference in VO2 = 3.50, 95%CI 2.62, 4.38, p =< 0.001). There was no difference in neurological participants' predicted mean VO2 pre- and post- 12 weeks of robotic therapy 0.45, 95%CI -0.20, 1.11, p = 0.15), although subgroup analysis revealed a greater change after 12 weeks of robotic therapy in those with stroke (MS: -0.06, 95%CI -0.78, 0.66, p = 0.85; stroke: 1.00, 95%CI 0.3, 1.69, p = 0.01; difference = 1.06, p = 0.04). Exercise in a free-standing robotic exoskeleton is not passive in healthy or neurologically impaired people, and those with stroke may derive more benefit than those with MS.
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Nova |
2020 |
Bivard A, Kleinig T, Churilov L, Levi C, Lin L, Cheng X, et al., 'Permeability Measures Predict Hemorrhagic Transformation after Ischemic Stroke', Annals of Neurology, 88 466-476 (2020) [C1]
Objective: We sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measu... [more]
Objective: We sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measures in ischemic stroke patients receiving alteplase only. Methods: A pixel-based analysis of pretreatment CT perfusion (CTP) was undertaken to define the optimal CTP permeability thresholds to predict the likelihood of HT. We then compared previously proposed predictors of HT using regression analyses and receiver operating characteristic curve analysis to produce an area under the curve (AUC). We compared AUCs using ¿2 analysis. Results: From 5 centers, 1,407 patients were included in this study; of these, 282 had HT. The cohort was split into a derivation cohort (1,025, 70% patients) and a validation cohort (382 patients or 30%). The extraction fraction (E) permeability map at a threshold of 30% relative to contralateral had the highest AUC at predicting any HT (derivation AUC 0.85, 95% confidence interval [CI], 0.79¿0.91; validation AUC 0.84, 95% CI 0.77¿0.91). The AUC improved when permeability was assessed within the acute perfusion lesion for the E maps at a threshold of 30% (derivation AUC 0.91, 95% CI 0.86¿0.95; validation AUC 0.89, 95% CI 0.86¿0.95). Previously proposed associations with HT and parenchymal hematoma showed lower AUC values than the permeability measure. Interpretation: In this large multicenter study, we have validated a highly accurate measure of HT prediction. This measure might be useful in clinical practice to predict hemorrhagic transformation in ischemic stroke patients before receiving alteplase alone. ANN NEUROL 2020;88:466¿476.
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Nova |
2020 |
Lillicrap T, Keragala CB, Draxler DF, Chan J, Ho H, Harman S, et al., 'Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples', FRONTIERS IN NEUROLOGY, 11 (2020)
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2020 |
Garcia-Esperon C, Soderhjelm Dinkelspiel F, Miteff F, Gangadharan S, Wellings T, O´Brien B, et al., 'Implementation of multimodal computed tomography in a telestroke network: Five-year experience', CNS Neuroscience and Therapeutics, 26 367-373 (2020) [C1]
Aims: Penumbral selection is best-evidence practice for thrombectomy in the 6-24¿hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal comput... [more]
Aims: Penumbral selection is best-evidence practice for thrombectomy in the 6-24¿hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal computed tomography (mCT) at the primary centre¿including noncontrast CT, CT perfusion, and CT angiography¿may enhance reperfusion therapy decision-making. We developed a network with five spoke primary stroke sites and assessed safety, feasibility, and influence of mCT in rural hospitals on decision-making for thrombolysis. Methods: Consecutive patients assessed via telemedicine from April 2013 to June 2018. Clinical outcomes were measured, and decision-making compared using theoretical models for reperfusion therapy applied without mCT guidance. Symptomatic intracranial hemorrhage (sICH) was assessed according to Safe Implementation of Treatments in Stroke Thrombolysis Registry criteria. Results: A total of 334 patients were assessed, 240 received mCT, 58 were thrombolysed (24.2%). The mean age of thrombolysed patients was 70¿years, median baseline National Institutes of Health Stroke Scale was 10 (IQR 7-18) and 23 (39.7%) had a large vessel occlusion. 1.7% had sICH and 3.5% parenchymal hematoma. Three months poststroke, 55% were independent, compared with 70% in the non-thrombolysed group. Conclusion: Implementation of CTP in rural centers was feasible and led to high thrombolysis rates with low rates of sICH.
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Nova |
2020 |
Cooper S, Bendinelli C, Bivard A, Parsons M, Balogh ZJ, 'Abnormalities on Perfusion CT and Intervention for Intracranial Hypertension in Severe Traumatic Brain Injury', JOURNAL OF CLINICAL MEDICINE, 9 (2020) [C1]
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Nova |
2020 |
Garcia-Esperon C, Spratt NJ, Gangadharan S, Miteff F, Bivard A, Lillicrap T, et al., 'Computed Tomography Perfusion Identifies Patients With Stroke With Impaired Cardiac Function', STROKE, 51 498-503 (2020) [C1]
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Nova |
2020 |
Levi CR, Attia JA, D'Este C, Ryan AE, Henskens F, Kerr E, et al., 'Cluster-Randomized Trial of Thrombolysis Implementation Support in Metropolitan and Regional Australian Stroke Centers: Lessons for Individual and Systems Behavior Change', JOURNAL OF THE AMERICAN HEART ASSOCIATION, 9 (2020) [C1]
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Nova |
2019 |
Cooper S, Bendinelli C, Bivard A, Parsons M, Balogh ZJ, 'When a Slice Is Not Enough! Comparison of Whole-Brain versus Standard Limited-Slice Perfusion Computed Tomography in Patients with Severe Traumatic Brain Injury', JOURNAL OF CLINICAL MEDICINE, 8 (2019) [C1]
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Nova |
2019 |
Tian H, Parsons MW, Levi CR, Lin L, Aviv RI, Spratt NJ, et al., 'Influence of occlusion site and baseline ischemic core on outcome in patients with ischemic stroke', Neurology, 92 E2626-E2643 (2019) [C1]
Objective: We assessed patient clinical outcomes based on occlusion location, focusing on distal occlusions to understand if occlusion location was an independent predictor of out... [more]
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%, p < 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, p < 0.001). There was no interaction between occlusion location and ischemic core (interaction coefficient 1.00, p = 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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Nova |
2019 |
Bisson DA, Mahmoudian D, Shatil AS, Waggass G, Zhang L, Levi C, et al., 'Single-phase CT angiography: collateral grade is independent of scan weighting', Neuroradiology, 61 19-28 (2019) [C1]
Purpose: Collateral grading may vary on single-phase CTA (sCTA) depending on whether the CTA is arterial (A), arteriovenous (AV), or venous (V) weighted. We studied the impact of ... [more]
Purpose: Collateral grading may vary on single-phase CTA (sCTA) depending on whether the CTA is arterial (A), arteriovenous (AV), or venous (V) weighted. We studied the impact of sCTA weighting on collateral grading using the Tan, MAAS, and Menon methods, and their ability to predict infarct and clinical outcome hypothesizing that AV-weighted sCTA should better predict these outcomes. Methods: Multicenter retrospective analysis of 212 patients undergoing baseline CTP/sCTA. sCTA weighting was determined by comparing ICA to torcula AV ratios with those from concomitant CTP time-density curves at peak arterial or venous contrast attenuation. A generalized linear mixed model investigated the predictive value for infarct volume or 90-day mRS of the three collateral scores stratified by sCTA weighting and adjusting for age, sex, clot burden score (CBS), and NIHSS. Bayesian information criterion (BIC) differences were calculated between the null and fitted models. Results: Mean age, baseline median NIHSS, ASPECTS, and onset to treatment time were 69.89 ± 14.45, 13 (6¿18), 10 (8¿10), and 128 (66¿181) minutes. sCTA scans were AV-weighted in 137/212 (65%) and A-weighted in 73 (34%). No association was demonstrated between sCTA weighting, hospital site, and sCTA technique. All collateral scores were related to infarct volume irrespective of sCTA weighting, with greatest fit with the regional leptomeningeal score (BIC 18.29, p = 0.0001). No association was shown between sCTA weighting, collateral grade, and clinical outcome. Conclusion: sCTA weighting did not significantly impact collateral grade using three common collateral scores or their ability to predict final infarct.
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Nova |
2019 |
Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al., 'Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke', The New England journal of medicine, 380 1795-1803 (2019) [C1]
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 suggeste... [more]
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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Nova |
2019 |
Alemseged F, Shah DG, Bivard A, Kleinig TJ, Yassi N, Diomedi M, et al., 'Cerebral blood volume lesion extent predicts functional outcome in patients with vertebral and basilar artery occlusion', International Journal of Stroke, 14 540-547 (2019) [C1]
Background: CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed ... [more]
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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Nova |
2019 |
Visser MM, Goodin P, Parsons MW, Lillicrap T, Spratt NJ, Levi CR, Bivard A, 'Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue', SCIENTIFIC REPORTS, 9 (2019) [C1]
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Nova |
2019 |
Tian H, Chen C, Garcia-Esperon C, Parsons MW, Lin L, Levi CR, Bivard A, 'Dynamic CT but Not Optimized Multiphase CT Angiography Accurately Identifies CT Perfusion Target Mismatch Ischemic Stroke Patients', FRONTIERS IN NEUROLOGY, 10 (2019) [C1]
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Nova |
2019 |
Vagal A, Wintermark M, Nael K, Bivard A, Parsons M, Grossman AW, Khatri P, 'Automated CT perfusion imaging for acute ischemic stroke: Pearls and pitfalls for real-world use', Neurology, 93 888-898 (2019) [C1]
Recent positive trials have thrust acute cerebral perfusion imaging into the routine evaluation of acute ischemic stroke. Updated guidelines state that in patients with anterior c... [more]
Recent positive trials have thrust acute cerebral perfusion imaging into the routine evaluation of acute ischemic stroke. Updated guidelines state that in patients with anterior circulation large vessel occlusions presenting beyond 6 hours from time last known well, advanced imaging selection including perfusion-based selection is necessary. Centers that receive patients with acute stroke must now have the capability to perform and interpret CT or magnetic resonance perfusion imaging or provide rapid transfer to centers with the capability of selecting patients for a highly impactful endovascular therapy, particularly in delayed time windows. Many stroke centers are quickly incorporating the use of automated perfusion processing software to interpret perfusion raw data. As CT perfusion (CTP) is being assimilated in real-world clinical practice, it is essential to understand the basics of perfusion acquisition, quantification, and interpretation. It is equally important to recognize the common technical and clinical diagnostic challenges of automated CTP including ischemic core and penumbral misclassifications that could result in underestimation or overestimation of the core and penumbra volumes. This review highlights the pitfalls of automated CTP along with practical pearls to address the common challenges. This is particularly tailored to aid the acute stroke clinician who must interpret automated perfusion studies in an emergency setting to make time-dependent treatment decisions for patients with acute ischemic stroke.
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Nova |
2019 |
Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, et al., 'Extending thrombolysis to 4·5 9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data', The Lancet, 394 139-147 (2019) [C1]
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 salv... [more]
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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Nova |
2019 |
Visser MM, Yassi N, Campbell BCV, Desmond PM, Davis SM, Spratt N, et al., 'White Matter Degeneration after Ischemic Stroke: A Longitudinal Diffusion Tensor Imaging Study', Journal of Neuroimaging, 29 111-118 (2019) [C1]
BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degenerat... [more]
BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degeneration after stroke. It is unclear whether white matter degeneration occurs throughout the whole brain, or whether patterns of degeneration occur more in specific brain areas. METHODS: We prospectively collected National Institutes of Health Stroke Scale (NIHSS) scores and diffusion tensor imaging (DTI) in patients with acute ischemic stroke within the first week after onset (baseline), and at 1 and 3 months. DTI was processed to produce maps of fractional anisotropy, apparent diffusion coefficients, and axial and radial diffusivity. DTI parameters in specified regions-of-interest corresponding to items on the NIHSS were calculated and changes over time were assessed using linear mixed-effect modeling. RESULTS: Seventeen patients were included in the study. Mean age (SD) was 71 (11.7) years, and median (IQR) baseline NIHSS 9 (5-13.3). Changes over time were observed in both visual cortices, contralesional primary motor cortex, premotor cortex, and superior temporal gyrus (P <.05). Changes in the ipsilesional motor cortex and inferior parietal lobule were only seen in patients with scores on the respective NIHSS-items (P <.05). No significant changes in global white matter diffusivity parameters were identified (P >.05). CONCLUSION: White matter changes after stroke may be localized rather than a global phenomenon.
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Nova |
2019 |
Visser MM, Maréchal B, Goodin P, Lillicrap TP, Garcia-Esperon C, Spratt NJ, et al., 'Predicting modafinil-treatment response in poststroke fatigue using brain morphometry and functional connectivity', Stroke, 50 602-609 (2019) [C1]
Background and Purpose - Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to... [more]
Background and Purpose - Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to be an effective agent in reducing poststroke fatigue; however, not all patients reported a significant decrease in fatigue with therapy. We sought to investigate clinical and radiological predictors of fatigue reduction with modafinil therapy in a stroke survivor cohort. Methods - Twenty-six participants with severe fatigue (multidimensional fatigue inventory-20 =60) underwent magnetic resonance imaging at baseline and during the last week of a 6-week treatment period of 200 mg modafinil taken daily. Resting-state functional magnetic resonance imaging and high-resolution structural imaging data were obtained, and functional connectivity and regional brain volumes within the fronto-striato-thalamic network were obtained. Linear regression analysis was used to identify predictors of modafinil-induced fatigue reduction. Results - Multiple regression analysis showed that baseline multidimensional fatigue inventory-20 score (ß=0.576, P=0.006) and functional connectivity between the dorsolateral prefrontal cortex and the caudate nucleus (ß=-0.424, P=0.008) were significant predictors of modafinil-associated decreases in poststroke fatigue (adjusted r2=0.52, area under the receiver operator characteristic curve=0.939). Conclusions - Fronto-striato-thalamic functional connectivity predicted modafinil response for poststroke fatigue. Fatigue in other neurological disease has been attributed to altered function of the fronto-striato-thalamic network and may indicate that poststroke fatigue has a similar mechanism to other neurological injury related fatigue. Self-reported fatigue in patients with normal fronto-striato-thalamic functional connectivity may have a different mechanism and require alternate therapeutic approaches.
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Nova |
2019 |
Postol N, Marquez J, Spartalis S, Bivard A, Spratt NJ, 'Do powered over-ground lower limb robotic exoskeletons affect outcomes in the rehabilitation of people with acquired brain injury?', Disability and Rehabilitation: Assistive Technology, 14 764-775 (2019) [C1]
Purpose: To assess the effects of lower limb robotic exoskeletons on outcomes in the rehabilitation of people with acquired brain injury. Materials and methods: A systematic revie... [more]
Purpose: To assess the effects of lower limb robotic exoskeletons on outcomes in the rehabilitation of people with acquired brain injury. Materials and methods: A systematic review of seven electronic databases was conducted. The primary outcome of interest was neuromuscular function. Secondary outcomes included quality of life, mood, acceptability and safety. Studies were assessed for methodological quality and recommendations were made using the GRADE system. Results: Of 2469 identified studies, 13 (n = 322) were included in the review. Five contained data suitable for meta-analysis. When the data were pooled, there were no differences between exoskeleton and control for 6-Minute Walk Test, Timed Up and Go or 10-Meter Walk Test. Berg Balance Scale outcomes were significantly better in controls (MD = 2.74, CI = 1.12¿4.36, p = 0.0009). There were no severe adverse events but drop-outs were 11.5% (n = 37). No studies reported the effect of robotic therapy on quality of life or mood. Methodological quality was on average fair (15.6/27 on Downs and Black Scale). Conclusions: Only small numbers of people with acquired brain injury had data suitable for analysis. The available data suggests no more benefit for gait or balance with robotic therapy than conventional therapy. However, some important outcomes have not been studied and further well-conducted research is needed to determine whether such devices offer benefit over conventional therapy, in particular subgroups of those with acquired brain injury.Implications for Rehabilitation There is adequate evidence to recommend that powered over-ground lower limb robotic exoskeletons should not be used clinically in those with ABI, and that use should be restricted to research. Further research (controlled trials) with dependent ambulators is recommended. Research of other outcomes such as acceptability, spasticity, sitting posture, cardiorespiratory and psychological function, should be considered.
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Nova |
2019 |
Hong L, Cheng X, Lin L, Bivard A, Ling Y, Butcher K, et al., 'The blood pressure paradox in acute ischemic stroke.', Ann Neurol, 85 331-339 (2019) [C1]
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Nova |
2019 |
Chen C, Parsons MW, Levi CR, Spratt NJ, Miteff F, Lin L, et al., 'Exploring the relationship between ischemic core volume and clinical outcomes after thrombectomy or thrombolysis', Neurology, 93 E283-E292 (2019) [C1]
ObjectiveTo assess whether complete reperfusion after IV thrombolysis (IVT-R) would result in similar clinical outcomes compared to complete reperfusion after endovascular thrombe... [more]
ObjectiveTo assess whether complete reperfusion after IV thrombolysis (IVT-R) would result in similar clinical outcomes compared to complete reperfusion after endovascular thrombectomy (EVT-R) in patients with a large vessel occlusion (LVO).MethodsEVT-R patients were matched by age, clinical severity, occlusion location, and baseline perfusion lesion volume to IVT-R patients from the International Stroke Perfusion Imaging Registry (INSPIRE). Only patients with complete reperfusion on follow-up imaging were included. The excellent clinical outcome rates at day 90 on the modified Rankin Scale (mRS) were compared between EVT-R vs IVT-R patients within quintiles of increasing baseline ischemic core and penumbral volumes.ResultsFrom INSPIRE, there were 141 EVT-R patients and 141 matched controls (IVT-R) who met the eligibility criteria. In patients with a baseline core <30 mL, EVT-R resulted in a lower odds of achieving an excellent outcome at day 90 compared to IVT-R (day 90 mRS 0-1 odds ratio 0.01, p < 0.001). The group with a baseline core <30 mL contained mostly patients with distal M1 or M2 occlusions, and good collaterals (p = 0.01). In patients with a baseline ischemic core volume >30 mL (internal carotid artery and mostly proximal M1 occlusions), EVT-R increased the odds of patients achieving an excellent clinical outcome (day 90 mRS 0-1 odds ratio 1.61, p < 0.001) and there was increased symptomatic intracranial hemorrhage in the IVT-R group with core >30 mL (20% vs 3% in EVT-R, p = 0.008).ConclusionFrom this observational cohort, LVO patients with larger baseline ischemic cores and proximal LVO, with poorer collaterals, clearly benefited from EVT-R compared to IVT-R alone. However, for distal LVO patients, with smaller ischemic cores and better collaterals, EVT-R was associated with a lower odds of favorable outcome compared to IVT-R alone.
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Nova |
2019 |
Chen C, Bivard A, Lin L, Levi CR, Spratt NJ, Parsons MW, 'Thresholds for infarction vary between gray matter and white matter in acute ischemic stroke: A CT perfusion study', Journal of Cerebral Blood Flow and Metabolism, 39 536-546 (2019) [C1]
We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65... [more]
We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65 sub-6 h ischemic stroke patients were assessed, who underwent acute computed tomography perfusion (CTP) and acute magnetic resonance imaging. CTP maps were generated by both standard singular value deconvolution (sSVD) and SVD with delay and dispersion correction (ddSVD). Analyses were undertaken to calculate sensitivity, specificity, and area under the curve (AUC) for each CTP threshold for core and penumbra in GM and WM. With sSVD, the core was best defined in GM by cerebral blood flow (CBF) < 30% (AUC: 0.73) and in WM by CBF < 20% (AUC: 0.67). With ddSVD, GM core was best defined by CBF < 35% (AUC: 0.75) and in WM by CBF < 25% (AUC: 0.68). A combined GM/WM threshold overestimated core compared to diffusion-weighted imaging, CBF < 25% from sSVD (1.88 ml, P = 0.007) and CBF < 30% from ddSVD (1.27 ml, P = 0.011). The perfusion lesion was best defined by T max > 5 s (AUC: 0.80) in GM and T max > 7 s (AUC: 0.75) in WM. With sSVD, a delay time (DT) > 3 s from ddSVD was the optimal for both GM (AUC: 0.78) and WM (AUC: 0.75). Using tissue-specific thresholds for GM/WM provides more accurate estimation of acute ischemic core.
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Nova |
2018 |
Lillicrap T, Garcia-Esperon C, Walker FR, Ong LK, Nilsson M, Spratt N, et al., 'Growth Hormone Deficiency Is Frequent After Recent Stroke', FRONTIERS IN NEUROLOGY, 9 (2018) [C1]
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Nova |
2018 |
Bivard A, Parsons M, 'Tissue is more important than time: insights into acute ischemic stroke from modern brain imaging', CURRENT OPINION IN NEUROLOGY, 31 23-27 (2018) [C1]
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Nova |
2018 |
Lin L, Bivard A, Kleinig T, Spratt NJ, Levi CR, Yang Q, Parsons MW, 'Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke', STROKE, 49 924-+ (2018) [C1]
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Nova |
2018 |
Ong LK, Chow WZ, Tebay C, Kluge M, Pietrogrande G, Zalewska K, et al., 'Growth Hormone Improves Cognitive Function After Experimental Stroke', STROKE, 49 1257-+ (2018) [C1]
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Nova |
2018 |
Zhou Y, Zhang R, Yan S, Zhang M, Chen Z, Hu H, et al., 'Identification of corticospinal tract lesion for predicting outcome in small perfusion stroke', Stroke, 49 2683-2691 (2018) [C1]
Background and Purpose: Whether patients with small perfusion lesions benefit from thrombolysis remains an uncertainty. We assessed acute ischemic stroke patients with a total per... [more]
Background and Purpose: Whether patients with small perfusion lesions benefit from thrombolysis remains an uncertainty. We assessed acute ischemic stroke patients with a total perfusion lesion of <15 mL and tested the hypothesis the pattern of corticospinal tract (CST) involvement might predict outcome in thrombolysis-eligible patients. Methods: We used a prospectively collected cohort of acute ischemic stroke patients being assessed for thrombolysis at 7 centers. Three neurologists categorized the presence of hypoperfusion and infarction within CST. Excellent outcome was defined as 90-day modified Rankin Scale score 0 to 1. Results: Of 2654 patients, 407 had a perfusion lesion <15 mL and were clinically eligible for thrombolysis (243 being treated). Median National Institutes of Health Stroke Scale was 5.0, and 312 (76.7%) patients achieved excellent outcome. Alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 72.0% versus untreated 83.5%; odds ratio, 0.541; P=0.025). For patients with CST hypoperfusion without CST infarction, alteplase treatment was an independent favorable factor for excellent outcome (alteplase-treated 75.6% versus untreated 47.1%; odds ratio, 4.096; P=0.045). Among patients with CST infarction, alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 30.6% versus untreated 88.9%; odds ratio, 0.002; P=0.003). Among patients without either CST hypoperfusion or CST infarction, alteplase treatment was not an independent influencing factor for excellent outcome (alteplase-treated 80.1% versus untreated 87.7%; P=0.258). Conclusions: Only patients with CST hypoperfusion without CST infarction among eligible acute ischemic stroke patients with small perfusion lesions could benefit from thrombolysis, which needs to be confirmed in future prospective studies. Patient selection, including an assessment of lesion location rather than purely lesion volume, may be ideal.
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Nova |
2018 |
Agarwal S, Bivard A, Warburton E, Parsons M, Levi C, 'Collateral response modulates the time-penumbra relationship in proximal arterial occlusions.', Neurology, 90 e316-e322 (2018) [C1]
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Nova |
2018 |
Bivard A, Lillicrap T, Marechal B, Garcia-Esperon C, Holliday E, Krishnamurthy V, et al., 'Transient Ischemic Attack Results in Delayed Brain Atrophy and Cognitive Decline', STROKE, 49 384-390 (2018) [C1]
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Nova |
2018 |
Reeves P, Edmunds K, Levi C, Lin L, Cheng X, Aviv R, et al., 'Cost-effectiveness of targeted thrombolytic therapy for stroke patients using multi-modal CT compared to usual practice', PLOS ONE, 13 (2018) [C1]
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Nova |
2018 |
Lillicrap TP, Levi CR, Holliday E, Parsons MW, Bivard A, 'Short- and Long-Term Efficacy of Modafinil at Improving Quality of Life in Stroke Survivors: A Post Hoc Sub Study of the Modafinil in Debilitating Fatigue After Stroke Trial', FRONTIERS IN NEUROLOGY, 9 (2018) [C1]
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Nova |
2018 |
Garcia-Esperon C, Bivard A, Levi C, Parsons M, 'Use of computed tomography perfusion for acute stroke in routine clinical practice: Complex scenarios, mimics, and artifacts', International Journal of Stroke, 13 469-472 (2018) [C1]
Background: Computed tomography perfusion is becoming widely accepted and used in acute stroke treatment. Computed tomography perfusion provides pathophysiological information nee... [more]
Background: Computed tomography perfusion is becoming widely accepted and used in acute stroke treatment. Computed tomography perfusion provides pathophysiological information needed in the acute decision making. Moreover, computed tomography perfusion shows excellent correlation with diffusion-weighted imaging and perfusion-weighted sequences to evaluate core and penumbra volumes. Multimodal computed tomography perfusion has practical advantages over magnetic resonance imaging, including availability, accessibility, and speed. Nevertheless, it bears some limitations, as the limited accuracy for small ischemic lesions or brainstem ischemia. Interpretation of the computed tomography perfusion maps can sometimes be difficult. The stroke neurologist faces complex or atypical cases of cerebral ischemia and stroke mimics, and needs to decide whether the ¿lesions¿ on computed tomography perfusion are real or artifact. Aims: The purpose of this review is, based on clinical cases from a comprehensive stroke center, to describe the added value that computed tomography perfusion can provide to the stroke physician in the acute phase before a treatment decision is made.
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Nova |
2018 |
Wannamaker R, Guinand T, Menon BK, Demchuk A, Goyal M, Frei D, et al., 'Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.', Stroke, 49 1426-1433 (2018) [C1]
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Nova |
2018 |
Tian H, Parsons MW, Levi CR, Cheng X, Aviv R, Spratt NJ, et al., 'Intravenous Thrombolysis May Not Improve Clinical Outcome of Acute Ischemic Stroke Patients Without a Baseline Vessel Occlusion', FRONTIERS IN NEUROLOGY, 9 (2018) [C1]
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Nova |
2017 |
Bivard A, Lillicrap T, Krishnamurthy V, Holliday E, Attia J, Pagram H, et al., 'MIDAS (Modafinil in Debilitating Fatigue after Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial', Stroke, 48 1293-1298 (2017) [C1]
Background and Purpose - This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue =3 months after stroke. We hypothes... [more]
Background and Purpose - This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue =3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. Methods - This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of =60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). Results - A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P<0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P=0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period (P>0.05). Conclusions - Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil.
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Nova |
2017 |
Demeestere J, Sewell C, Rudd J, Ang T, Jordan L, Wills J, et al., 'The establishment of a telestroke service using multimodal CT imaging decision assistance: Turning on the fog lights ', Journal of Clinical Neuroscience, 37 1-5 (2017) [C1]
Telestroke services have been shown to increase stroke therapy access in rural areas. The implementation of advanced CT imaging for patient assessment may improve patient selectio... [more]
Telestroke services have been shown to increase stroke therapy access in rural areas. The implementation of advanced CT imaging for patient assessment may improve patient selection and detection of stroke mimics in conjunction with telestroke. We implemented a telestroke service supported by multimodal CT imaging in a rural hospital in Australia. Over 21¿months we conducted an evaluation of service activation, thrombolysis rates and use of multimodal imaging to assess the feasibility of the service. Rates of symptomatic intracranial haemorrhage and 90-day modified Rankin Score were used as safety outcomes. Fifty-eight patients were assessed using telestroke, of which 41 were regarded to be acute ischemic strokes and 17 to be stroke mimics on clinical grounds. Of the 41 acute stroke patients, 22 patients were deemed eligible for thrombolysis. Using multimodal CT imaging, 8 more patients were excluded from treatment because of lack of treatment target. Multimodal imaging failed to be obtained in one patient. For the 14 treated patients, median door-imaging time was 38¿min. Median door-treatment time was 91¿min. A 90-day mRS ¿2 was achieved in 40% of treated patients. We conclude that a telestroke service using advanced CT imaging for therapy decision assistance can be successfully implemented in regional Australia and can be used to guide acute stroke treatment decision-making and improve access to thrombolytic therapy. Efficiency and safety is comparable to established telestroke services.
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Nova |
2017 |
Pagram H, Bivard A, Lincz LF, Levi C, 'Immunity and stroke, the hurdles of stroke research translation', International Journal of Stroke, 12 123-131 (2017) [C1]
Immunomodulatory therapies after stroke have the potential to provide clinical benefit to a subset of patients, but risk subverting the protective, healing aspects of the innate i... [more]
Immunomodulatory therapies after stroke have the potential to provide clinical benefit to a subset of patients, but risk subverting the protective, healing aspects of the innate immune response. Neutrophils clear necrotic cerebral tissue and are important in immunomodulation, but can also contribute to tissue injury. Human trials for immunomodulatory stroke treatments in the sub-acute time frame have attempted to prevent peripheral neutrophil infiltration, but none have been successful and one trial demonstrated harm. These unselected trials had broad inclusion criteria and appear to not have had a specific treatment target. Unfortunately, due to the heterogeneous nature of brain ischemia in humans resulting in variation in clinical severity, the negative effect of thrombolytic drugs on the blood¿brain barrier, and the heterogeneity of immune response, it may only be a subset of stroke patients who can realistically benefit from immunomodulation therapies. Translational research strategies require both an understanding of lab practices which create highly controlled environments in contrast to clinical practice where the diagnosis of stroke does not require the identification of a vessel occlusion. These differences between lab and clinical practices can be resolved through the integration of appropriate patient selection criteria and use of advanced imaging and ridged patient selection practices in clinical trials which will be an important part to the success of any future trials of translational research such as immunomodulation.
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Nova |
2017 |
Chen C, Parsons MW, Clapham M, Oldmeadow C, Levi CR, Lin L, et al., 'Influence of penumbral reperfusion on clinical outcome depends on baseline ischemic core volume', Stroke, 48 2739-2745 (2017) [C1]
Background and Purpose: In alteplase-treated patients with acute ischemic stroke, we investigated the relationship between penumbral reperfusion at 24 hours and clinical outcomes,... [more]
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; R2, 0.28; P<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; R2, 0.55; P<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 (R2, 0.31; P<0.0001). This association was again stronger after adjustment for baseline ischemic core volume (R2, 0.41; P<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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Nova |
2017 |
Demeestere J, Garcia-Esperon C, Garcia-Bermejo P, Ombelet F, Mcelduff P, Bivard A, et al., 'Evaluation of hyperacute infarct volume using ASPECTS and brain CT perfusion core volume', Neurology, 88 2248-2253 (2017) [C1]
Objective: To compare the accuracy of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and CT perfusion to detect established infarction in acute anterior circulat... [more]
Objective: To compare the accuracy of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and CT perfusion to detect established infarction in acute anterior circulation stroke. Methods: We performed an observational study in 59 acute anterior circulation ischemic stroke patients who underwent brain noncontrast CT, CT perfusion, and MRI within 100 minutes from CT imaging. ASPECTS scores were calculated by 4 blinded vascular neurologists. The accuracy of ASPECTS and CT perfusion core volume to detect an acute MRI diffusion lesion of =70 mL was evaluated using receiver operating characteristics analysis and optimum cutoff values were calculated using Youden J. Results: Median ASPECTS score was 8 (interquartile range [IQR] 5-9). Median CT perfusion core volume was 22 mL (IQR 10.4-71.9). Median MRI diffusion lesion volume was 24.5 mL (IQR 10-63.9). No significant difference was found between the accuracy of CT perfusion and ASPECTS (c statistic 0.95 vs 0.87, p value for difference = 0.17). The optimum ASPECTS cutoff score to detect a diffusion-weighted imaging lesion =70 mL was <7 (sensitivity 0.74, specificity 0.86, Youden J = 0.60) and the optimum CT perfusion core volume cutoff was =50 mL (sensitivity 0.86, specificity 0.97, Youden J = 0.84). The CT perfusion core lesion covered a median of 100% (IQR 86%-100%) of the acute MRI lesion volume (Pearson R = 0.88; R 2 = 0.77). Conclusions: We found no significant difference between the accuracy of CT perfusion and ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.
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Nova |
2017 |
Bivard A, Huang X, Levi CR, Spratt N, Campbell BCV, Cheripelli BK, et al., 'Tenecteplase in ischemic stroke offers improved recanalization', Neurology, 89 62-67 (2017) [C1]
Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated... [more]
Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with tenecteplase compared to alteplase. Methods: Pooled clinical and imaging data from 2 phase 2 randomized trials comparing tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs). Results: From 146 pooled patients, 69 had a TICI 0/1 occlusion overall at baseline. Tenecteplase-treated patients with a complete vessel occlusion had greater complete recanalization rates at 24 hours (71% for tenecteplase vs 43% for alteplase, p < 0.001). Patients with a TICI 0/1 occlusion who were treated with tenecteplase also showed greater early clinical improvement (median NIHSS change with tenecteplase was 9, interquartile range [IQR] 6, alteplase 1, IQR 1, p = 0.001) and higher rates of favorable 90-day outcomes (mRS 0-1 of tenecteplase compared with alteplase, OR 4.82, 95% confidence interval 1.02-7.84, p = 0.05). Conclusions: Tenecteplase may offer greater recanalization efficacy compared to alteplase, possibly exaggerated in patients with complete vessel occlusions on baseline CTA.
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Nova |
2017 |
Gao J, Parsons MW, Kawano H, Levi CR, Evans TJ, Lin L, Bivard A, 'Visibility of CT early ischemic change is significantly associated with time from stroke onset to baseline scan beyond the first 3 hours of stroke onset', Journal of Stroke, 19 340-346 (2017) [C1]
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Nova |
2017 |
Levi CR, Demeestere J, Garcia-Esperon C, Garcia-Bermejo P, Ombelet F, McElduff P, et al., 'AUTHOR RESPONSE: EVALUATION OF HYPERACUTE INFARCT VOLUME USING ASPECTS AND BRAIN CT PERFUSION CORE VOLUME', NEUROLOGY, 89 2398-2399 (2017)
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2017 |
Lillicrap T, Tahtali M, Neely A, Wang X, Bivard A, Lueck C, 'A model based on the Pennes bioheat transfer equation is valid in normal brain tissue but not brain tissue suffering focal ischaemia.', Australasian physical & engineering sciences in medicine, 40 841-850 (2017) [C1]
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Nova |
2017 |
Lin L, Cheng X, Bivard A, Levi CR, Dong Q, Parsons MW, 'Quantifying reperfusion of the ischemic region on whole-brain computed tomography perfusion', Journal of Cerebral Blood Flow and Metabolism, 37 2125-2136 (2017) [C1]
To derive the reperfusion index best predicting clinical outcome of ischemic stroke patients, we retrospectively analysed the acute and 24-h computed tomography perfusion data of ... [more]
To derive the reperfusion index best predicting clinical outcome of ischemic stroke patients, we retrospectively analysed the acute and 24-h computed tomography perfusion data of 116 patients, collected from two centres equipped with whole-brain computed tomography perfusion. Reperfusion index was defined by the percentage of the ischemic region reperfused from acute to 24-h computed tomography perfusion. Recanalization was graded by arterial occlusive lesion system. Receiver operator characteristic analysis was performed to assess the prognostic value of reperfusion and recanalization in predicting good clinical outcome, defined as modified Rankin Score of 0¿2 at 90 days. Among previous reported reperfusion measurements, reperfusion of the Tmax>6 s region resulted in higher prognostic value than recanalization at predicting good clinical outcome (area under the curve = 0.88 and 0.74, respectively, p = 0.002). Successful reperfusion of the Tmax>6 s region (=60%) had 89% sensitivity and 78% specificity in predicting good clinical outcome. A reperfusion index defined by Tmax>2 s or by mean transit time>145% had much lower area under the curve in comparison to Tmax>6 s measurement (p < 0.001 and p = 0.003, respectively), and had no significant difference to recanalization at predicting clinical outcome (p = 0.58 and 0.63, respectively). In conclusion, reperfusion index calculated by Tmax>6 s is a stronger predictor of clinical outcome than recanalization or other reperfusion measures.
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Nova |
2017 |
Bivard A, Levi C, Lin L, Cheng X, Aviv R, Spratt NJ, et al., 'Validating a Predictive Model of Acute Advanced Imaging Biomarkers in Ischemic Stroke', Stroke, 48 645-650 (2017) [C1]
Background and Purpose - Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. This st... [more]
Background and Purpose - Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. This study aimed to derive and validate a predictive model for functional outcome based on acute clinical and advanced imaging measures. Methods - A database of prospectively collected sub-4.5 hour patients with ischemic stroke being assessed for thrombolysis from 5 centers who had computed tomographic perfusion and computed tomographic angiography before a treatment decision was assessed. Individual variable cut points were derived from a classification and regression tree analysis. The optimal cut points for each assessment variable were then used in a backward logic regression to predict modified Rankin scale (MRS) score of 0 to 1 and 5 to 6. The variables remaining in the models were then assessed using a receiver operating characteristic curve analysis. Results - Overall, 1519 patients were included in the study, 635 in the derivation cohort and 884 in the validation cohort. The model was highly accurate at predicting MRS score of 0 to 1 in all patients considered for thrombolysis therapy (area under the curve [AUC] 0.91), those who were treated (AUC 0.88) and those with recanalization (AUC 0.89). Next, the model was highly accurate at predicting MRS score of 5 to 6 in all patients considered for thrombolysis therapy (AUC 0.91), those who were treated (0.89) and those with recanalization (AUC 0.91). The odds ratio of thrombolysed patients who met the model criteria achieving MRS score of 0 to 1 was 17.89 (4.59-36.35, P<0.001) and for MRS score of 5 to 6 was 8.23 (2.57-26.97, P<0.001). Conclusions - This study has derived and validated a highly accurate model at predicting patient outcome after ischemic stroke.
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Nova |
2017 |
Bhaskar S, Stanwell P, Bivard A, Spratt N, Walker R, Kitsos GH, et al., 'The influence of initial stroke severity on the likelihood of unfavourable clinical outcome and death at 90 days following acute ischemic stroke: A tertiary hospital stroke register study', Neurology India, 65 1252-1259 (2017) [C1]
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Nova |
2017 |
Demeestere J, Garcia-Esperon C, Lin L, Bivard A, Ang T, Smoll NR, et al., 'Validation of the National Institutes of Health Stroke Scale-8 to Detect Large Vessel Occlusion in Ischemic Stroke', Journal of Stroke and Cerebrovascular Diseases, 26 1419-1426 (2017) [C1]
Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy.... [more]
Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy. Aims We aimed to assess the accuracy of an existing 8-item stroke scale (National Institutes of Health Stroke Scale-8 [NIHSS-8]) for identification of patients with acute stroke with LVO. Methods We retrospectively calculated NIHSS-8 scores in a population of consecutive patients with presumed acute stroke assessed by emergency medical services (EMS). LVO was identified on admission computed tomography angiography. Accuracy to identify LVO was calculated using receiver operating characteristics analysis. We used weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS-8 score between the EMS and the hospital stroke team on a prospectively evaluated subgroup. Results Of the 551 included patients, 381 had a confirmed ischemic stroke and 136 patients had an LVO. NIHSS scores were significantly higher in patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score reliably predicted the presence of LVO (area under the receiver operating characteristic curve.82). The optimum NIHSS-8 cutoff of 8 or more had a sensitivity of.81, specificity of.75, and Youden index of.56 for prediction of LVO. The EMS and the stroke team reached substantial agreement (¿ =.69). Conclusions Accuracy of the NIHSS-8 to identify LVO in a population of patients with suspected acute stroke is comparable to existing prehospital stroke scales. The scale can be performed by EMS with reasonable reliability. Further validation in the field is needed to assess accuracy of the scale to identify patients with LVO eligible for endovascular treatment in a prehospital setting.
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Nova |
2017 |
Bhaskar S, Bivard A, Parsons M, Nilsson M, Attia JR, Stanwell P, Levi C, 'Delay of late-venous phase cortical vein filling in acute ischemic stroke patients: Associations with collateral status', Journal of Cerebral Blood Flow and Metabolism, 37 671-682 (2017) [C1]
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Nova |
2017 |
Bivard A, Huang X, McElduff P, Levi CR, Campbell BCV, Cheripelli BK, et al., 'Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials', Circulation, 135 440-448 (2017) [C1]
Background: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the... [more]
Background: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. Methods: We investigated whether tenecteplase-Treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-Treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group. Results: Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-Treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: Tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0-1: odds ratio, 1.77; 95% confidence interval, 0.89-3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: Tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0-1: odds ratio, 2.33; 95% confidence interval, 1.13-5.94; P=0.032) than those treated with alteplase. Conclusions: Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion-defined target mismatch. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926. URL: https://www.anzctr.org.au. Unique identifier: ACTRN12608000466347.
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Nova |
2017 |
Alemseged F, Shah DG, Diomedi M, Sallustio F, Bivard A, Sharma G, et al., 'The Basilar Artery on Computed Tomography Angiography Prognostic Score for Basilar Artery Occlusion', Stroke, 48 631-637 (2017) [C1]
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Nova |
2017 |
Bivard A, Muir K, Parsons M, 'Response by Bivard et al to Letter Regarding Article, "Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials"', CIRCULATION, 135 E1141-E1142 (2017)
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2017 |
Bivard A, Levi C, Parsons M, 'Response by Bivard et al to Letter Regarding Article, "Validating a Predictive Model of Acute Advanced Imaging Biomarkers in Ischemic Stroke"', STROKE, 48 E226-E226 (2017)
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2017 |
Bhaskar S, Bivard A, Stanwell P, Parsons M, Attia JR, Nilsson M, Levi C, 'Baseline collateral status and infarct topography in post-ischaemic perilesional hyperperfusion: An arterial spin labelling study', Journal of Cerebral Blood Flow and Metabolism, 37 1148-1162 (2017) [C1]
Focal hyperperfusion after acute ischaemic stroke could be of prognostic value depending upon its spatial localisation and temporal dynamics. Factors associated with late stage (1... [more]
Focal hyperperfusion after acute ischaemic stroke could be of prognostic value depending upon its spatial localisation and temporal dynamics. Factors associated with late stage (12-24 h) perilesional hyperperfusion, identified using arterial spin labelling, are poorly defined. A prospective cohort of acute ischaemic stroke patients presenting within 4.5 h of symptom onset were assessed with multi-modal computed tomography acutely and magnetic resonance imaging at 24 ± 8 h. Multivariate logistic regression analysis and receiver operating characteristics curves were used. One hundred and nineteen hemispheric acute ischaemic stroke patients (mean age = 71 ± 12 years) with 24 h arterial spin labelling imaging were included. Forty-Two (35.3%) patients showed perilesional hyperperfusion on arterial spin labelling at 24 h. Several factors were independently associated with perilesional hyperperfusion: good collaterals (71% versus 29%, P < 0.0001; OR = 5, 95% CI = [1.6, 15.7], P = 0.005), major reperfusion (81% versus 48%, P = < 0.0001; OR = 7.5, 95% CI = [1.6, 35.1], P = 0.01), penumbral salvage (76.2% versus 47%, P = 0.002; OR = 6.6, 95% CI = [1.8, 24.5], P = 0.004), infarction in striatocapsular (OR = 9.5, 95% CI = [2.6, 34], P = 0.001) and in cortical superior division middle cerebral artery (OR = 4.7, 95% CI = [1.4, 15.7], P = 0.012) territory. The area under the receiver operating characteristic curve was 0.91. Our results demonstrate good arterial collaterals, major reperfusion, penumbral salvage, and infarct topographies involving cortical superior middle cerebral artery and striatocapsular are associated with perilesional hyperperfusion.
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Nova |
2017 |
Bendinelli C, Cooper S, Evans T, Bivard A, Pacey D, Parson M, Balogh ZJ, 'Perfusion Abnormalities are Frequently Detected by Early CT Perfusion and Predict Unfavourable Outcome Following Severe Traumatic Brain Injury', World Journal of Surgery, 41 2512-2520 (2017) [C1]
Background: In patients with severe traumatic brain injury (TBI), early CT perfusion (CTP) provides additional information beyond the non-contrast CT (NCCT) and may alter clinical... [more]
Background: In patients with severe traumatic brain injury (TBI), early CT perfusion (CTP) provides additional information beyond the non-contrast CT (NCCT) and may alter clinical management. We hypothesized that this information may prognosticate functional outcome. Methods: Five-year prospective observational study was performed in a level-1 trauma centre on consecutive severe TBI patients. CTP (obtained in conjunction with first routine NCCT) was interpreted as: abnormal, area of altered perfusion more extensive than on NCCT, and the presence of ischaemia. Six months Glasgow Outcome Scale-Extended of four or less was considered an unfavourable outcome. Logistic regression analysis of CTP findings and core variables [preintubation Glasgow Coma Scale (GCS), Rotterdam score, base deficit, age] was conducted using Bayesian model averaging to identify the best predicting model for unfavourable outcome. Results: Fifty patients were investigated with CTP (one excluded for the absence of TBI) [male: 80%, median age: 35 (23¿55), prehospital intubation: 7 (14.2%); median GCS: 5 (3¿7); median injury severity score: 29 (20¿36); median head and neck abbreviated injury scale: 4 (4¿5); median days in ICU: 10 (5¿15)]. Thirty (50.8%) patients had an unfavourable outcome. GCS was a moderate predictor of unfavourable outcome (AUC¿=¿0.74), while CTP variables showed greater predictive ability (AUC for abnormal CTP¿=¿0.92; AUC for area of altered perfusion more extensive than NCCT¿=¿0.83; AUC for the presence of ischaemia¿=¿0.81). Conclusion: Following severe TBI, CTP performed at the time of the first follow-up NCCT, is a non-invasive and extremely valuable tool for early outcome prediction. The potential impact on management and its cost effectiveness deserves to be evaluated in large-scale studies. Level of evidence III: Prospective study.
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Nova |
2017 |
Bivard A, Kleinig T, Miteff F, Butcher K, Lin L, Levi C, Parsons M, 'Ischemic core thresholds change with time to reperfusion: A case control study', Annals of Neurology, 82 995-1003 (2017) [C1]
Introduction: We aimed to identify whether acute ischemic stroke patients with known complete reperfusion after thrombectomy had the same baseline computed tomography perfusion (C... [more]
Introduction: We aimed to identify whether acute ischemic stroke patients with known complete reperfusion after thrombectomy had the same baseline computed tomography perfusion (CTP) ischemic core threshold to predict infarction as thrombolysis patients with complete reperfusion. Methods: Patients who underwent thrombectomy were matched by age, clinical severity, occlusion location, and baseline perfusion lesion volume to patients who were treated with intravenous alteplase alone from the International Stroke Perfusion Imaging Registry. A pixel-based analysis of coregistered pretreatment CTP and 24-hour diffusion-weighted imaging (DWI) was then undertaken to define the optimum CTP thresholds for the ischemic core. Results: There were 132 eligible thrombectomy patients and 132 matched controls treated with alteplase alone. Baseline National Institutes of Health Stroke Scale (median, 15; interquartile range [IQR], 11¿19), age (median, 65; IQR, 59¿80), and time to intravenous treatment (median, 153 minutes; IQR, 82¿315) were well matched (all p > 0.05). Despite similar baseline CTP ischemic core volumes using the previously validated measure (relative cerebral blood flow [rCBF], <30%), thrombectomy patients had a smaller median 24-hour infarct core of 17.3ml (IQR, 11.3¿32.8) versus 24.3ml (IQR, 16.7¿42.2; p = 0.011) in alteplase-treated controls. As a result, the optimal threshold to define the ischemic core in thrombectomy patients was rCBF <20% (area under the curve [AUC], 0.89; 95% CI, 0.84, 0.94), whereas in alteplase controls the optimal ischemic core threshold remained rCBF <30% (AUC, 0.83; 95% CI, 0.77, 0.85). Interpretation: Thrombectomy salvaged tissue with lower CBF, likely attributed to earlier reperfusion. For patients who achieve rapid reperfusion, a stricter rCBF threshold to estimate the ischemic core should be considered. Ann Neurol 2017;82:995¿1003.
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Nova |
2017 |
Bivard A, Lincz LF, Maquire J, Parsons M, Levi C, 'Platelet microparticles: a biomarker for recanalization in rtPA-treated ischemic stroke patients', ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 4 175-179 (2017) [C1]
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Nova |
2017 |
Kawano H, Bivard A, Lin L, Ma H, Cheng X, Aviv R, et al., 'Perfusion computed tomography in patients with stroke thrombolysis', Brain, 140 684-691 (2017) [C1]
Stroke shortens an individual¿s disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variabl... [more]
Stroke shortens an individual¿s disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variables (e.g. ischaemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. We used data from a prospectively collected international, multicentre, observational registry of acute ischaemic stroke patients who had perfusion computed tomography and computed tomography angiography before treatment with intravenous alteplase. Baseline perfusion computed tomography and follow-up magnetic resonance imaging were analysed to derive the baseline penumbra volume, baseline ischaemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on Disability-Adjusted Life Year. Clinical variables were age, sex, National Institutes of Health Stroke Scale score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate disability-adjusted life-year due to stroke, such that 1 year of disability-adjusted life-year equates to 1 year of healthy life lost due to stroke. There were 772 patients receiving alteplase therapy. The number of disability-adjusted life-year days lost per 1 ml of baseline ischaemic core volume was 17.5 (95% confidence interval, 13.2¿21.9 days, P 5 0.001). For every millilitre of penumbra salvaged, 7.2 days of disability-adjusted life-year days were saved (b = 7.2, 95% confidence interval, 10.4 to 4.1 days, P 5 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3¿7.5 days, P = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not significantly associated with savings in disability-adjusted life-year days. Pretreatment perfusion computed tomography can (independently of clinical variables) predict significant gains, or loss, of disability-free life in patients undergoing reperfusion therapy for stroke. The effect of earlier treatment on disability-free life appears explained by salvage of penumbra, particularly when the ischaemic core is not too large.
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Nova |
2016 |
Kawano H, Levi C, Inatomi Y, Pagram H, Kerr E, Bivard A, et al., 'International benchmarking for acute thrombolytic therapy implementation in Australia and Japan', Journal of Clinical Neuroscience, 29 87-91 (2016) [C1]
Although a wide range of strategies have been established to improve intravenous tissue plasminogen activator (IV-tPA) treatment rates, international benchmarking has not been reg... [more]
Although a wide range of strategies have been established to improve intravenous tissue plasminogen activator (IV-tPA) treatment rates, international benchmarking has not been regularly used as a systems improvement tool. We compared acute stroke codes (ASC) between two hospitals in Australia and Japan to study the activation process and potentially improve the implementation of thrombolysis. Consecutive patients who were admitted to each hospital via ASC were prospectively collected. We compared IV-tPA rates, factors contributing to exclusion from IV-tPA, and pre- and in-hospital process of care. IV-tPA treatment rates were significantly higher in the Australian hospital than in the Japanese (41% versus 25% of acute ischaemic stroke patients, p = 0.0016). In both hospitals, reasons for exclusion from IV-tPA treatment were intracerebral haemorrhage, mild symptoms, and stroke mimic. Patients with baseline National Institutes of Health Stroke Scale score =5 were more likely to be excluded from IV-tPA in the Japanese hospital. Of patients treated with IV-tPA, the door-to-needle time (median, 63 versus 54 minutes, p = 0.0355) and imaging-to-needle time (34 versus 27 minutes, p = 0.0220) were longer in the Australian hospital. Through international benchmarking using cohorts captured under ASC, significant differences were noted in rates of IV-tPA treatment and workflow speed. This variation highlights opportunity to improve and areas to focus targeted practice improvement strategies.
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Nova |
2016 |
Bivard A, Cheng X, Lin LT, Levi C, Spratt N, Kleinig T, et al., 'Global White Matter Hypoperfusion on CT Predicts Larger Infarcts and Hemorrhagic Transformation after Acute Ischemia', CNS Neuroscience and Therapeutics, 22 238-243 (2016) [C1]
Introduction: Presence of white matter hyperintensity (WMH) on MRI is a marker of cerebral small vessel disease and is associated with increased small vessel stroke and increased ... [more]
Introduction: Presence of white matter hyperintensity (WMH) on MRI is a marker of cerebral small vessel disease and is associated with increased small vessel stroke and increased risk of hemorrhagic transformation (HT) after thrombolysis. Aim: We sought to determine whether white matter hypoperfusion (WMHP) on perfusion CT (CTP) was related to WMH, and if WMHP predisposed to acute lacunar stroke subtype and HT after thrombolysis. Methods: Acute ischemic stroke patients within 12 h of symptom onset at 2 centers were prospectively recruited between 2011 and 2013 for the International Stroke Perfusion Imaging Registry. Participants routinely underwent baseline CT imaging, including CTP, and follow-up imaging with MRI at 24 h. Results: Of 229 ischemic stroke patients, 108 were Caucasians and 121 Chinese. In the contralateral white matter, patients with acute lacunar stroke had lower cerebral blood flow (CBF) and cerebral blood volume (CBV), compared to those with other stroke subtypes (P = 0.041). There were 46 patients with HT, and WMHP was associated with increased risk of HT (R 2 = 0.417, P = 0.002). Compared to previously reported predictors of HT, WMHP performed better than infarct core volume (R 2 = 0.341, P = 0.034), very low CBV volume (R 2 = 0.249, P = 0.026), and severely delayed perfusion (Tmax>14 second R 2 = 0.372, P = 0.011). Patients with WMHP also had larger acute infarcts and increased infarct growth compared to those without WMHP (mean 28 mL vs. 13 mL P < 0.001). Conclusion: White matter hypoperfusion remote to the acutely ischemic region on CTP is a marker of small vessel disease and was associated with increased HT, larger acute infarct cores, and greater infarct growth.
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Nova |
2016 |
Bhaskar S, Bivard A, Stanwell P, Attia JR, Parsons M, Nilsson M, Levi C, 'Association of Cortical Vein Filling with Clot Location and Clinical Outcomes in Acute Ischaemic Stroke Patients', SCIENTIFIC REPORTS, 6 (2016) [C1]
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Nova |
2016 |
Lees KR, Khatri P, Alexandrov AV, Bivard A, Boltze J, Broderick JP, et al., 'Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke', Stroke, 47 2154-2159 (2016) [C1]
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2016 |
Lillicrap T, Krishnamurthy V, Attia J, Nilsson M, Levi CR, Parsons MW, Bivard A, 'Modafinil In Debilitating fatigue After Stroke (MIDAS): study protocol for a randomised, double-blinded, placebo-controlled, crossover trial', TRIALS, 17 (2016)
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2016 |
Huynh DC, Parsons MW, Wintermark M, Vagal A, d Esterre CD, Vitorino R, et al., 'Can CT perfusion accurately assess infarct core?', Neurovascular Imaging, 2 (2016) [C1]
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Nova |
2016 |
Warach SJ, Luby M, Albers GW, Bammer R, Bivard A, Campbell BCV, et al., 'Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities', Stroke, 47 1389-1398 (2016) [C1]
Background and Purpose - The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the Americ... [more]
Background and Purpose - The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. Methods - This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. Results - The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. Conclusions - Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.
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Nova |
2016 |
Yassi N, Campbell BCV, Moffat BA, Steward C, Churilov L, Parsons MW, et al., 'Association between baseline peri-infarct magnetic resonance spectroscopy and regional white matter atrophy after stroke', Neuroradiology, 58 3-10 (2016) [C1]
Introduction: Cerebral atrophy after stroke is associated with poor functional outcome. The prediction and prevention of post-stroke brain atrophy could therefore represent a targ... [more]
Introduction: Cerebral atrophy after stroke is associated with poor functional outcome. The prediction and prevention of post-stroke brain atrophy could therefore represent a target for neurorestorative therapies. We investigated the associations between peri-infarct metabolite concentrations measured by quantitative MRS and brain volume change in the infarct hemisphere after stroke. Methods: Twenty patients with ischemic stroke were enrolled. Patients underwent 3T-MRI within 1¿week of onset, and at 1 and 3¿months. At the baseline scan, an MRS voxel was placed manually in the peri-infarct area and another in the corresponding contralateral region. Volumetric analysis of T1 images was performed using two automated processing packages. Changes in gray and white matter volume were assessed as percentage change between 1 and 3¿months. Results: Mean concentrations (institutional units) of N-acetylaspartic acid (NAA) (6.1 vs 7.0, p = 0.039), total creatine (Cr+PCr) (5.4 vs 5.8, p = 0.043), and inositol (4.5 vs 5.0, p = 0.014), were significantly lower in the peri-infarct region compared with the contralateral hemisphere. There was a significant correlation between baseline peri-infarct NAA and white matter volume change in the infarct hemisphere between 1 and 3¿months, with lower NAA being associated with subsequent white matter atrophy (Spearman¿s rho = 0.66, p = 0.010). The baseline concentration of Cr+PCr was also significantly correlated with white matter atrophy in the infarct hemisphere (Spearman¿s rho = 0.59, p = 0.027). Both of these associations were significant after adjustment for the false discovery rate and were validated using the secondary volumetric method. Conclusion: MRS may be useful in the prediction of white matter atrophy post-stroke and in the testing of novel neurorestorative therapies.
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Nova |
2016 |
Pagram H, Bivard A, Lincz LF, Levi C, 'Peripheral Immune Cell Counts and Advanced Imaging as Biomarkers of Stroke Outcome.', Cerebrovasc Dis Extra, 6 120-128 (2016) [C1]
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Nova |
2016 |
Kawano H, Bivard A, Lin L, Spratt NJ, Miteff F, Parsons MW, Levi CR, 'Relationship between Collateral Status, Contrast Transit, and Contrast Density in Acute Ischemic Stroke', Stroke, 47 742-749 (2016) [C1]
Background and Purpose-Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collate... [more]
Background and Purpose-Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collateral status on acute imaging is uncertain. We aimed to determine the relationship between visual collateral status, quantitative collateral assessments, baseline computed tomographic perfusion measures, and tissue outcomes on follow-up imaging. Methods-Sixty-six consecutive patients with acute ischemic stroke clinically eligible for recanalization therapy and with M1 or M2 middle cerebral artery occlusion were evaluated. We compared the visual collateral scoring with measures of contrast peak time delay and contrast peak density. We also compared these measures for their ability to predict perfusion lesion and infarct core volumes, final infarct, and infarct growth. Results-Shorter contrast peak time delay (P=0.041) and higher contrast peak density (P=0.002) were associated with good collateral status. Shorter contrast peak time delay correlated with higher contrast peak density (ß=-4.413; P=0.037). In logistic regression analysis after adjustment for age, sex, onset-computed tomographic time, and occlusion site, higher contrast peak density was independently associated with good collateral status (P=0.009). Multiple regression analysis showed that higher contrast peak density was an independent predictor of smaller perfusion lesion volume (P=0.029), smaller ischemic core volume (P=0.044), smaller follow-up infarct volume (P=0.005), and smaller infarct growth volume (P=0.010). Conclusions-Visual collateral status, contrast peak density, and contrast peak time delay were inter-related, and good collateral status was strongly associated with contrast peak density. Contrast peak density in collateral vessel may be an important factor in tissue fate in acute ischemic stroke.
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Nova |
2016 |
Lin L, Bivard A, Krishnamurthy V, Levi CR, Parsons MW, 'Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core', RADIOLOGY, 279 876-887 (2016) [C1]
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Nova |
2016 |
Bivard A, Lou M, Levi CR, Krishnamurthy V, Cheng X, Aviv RI, et al., 'Too good to treat? ischemic stroke patients with small computed tomography perfusion lesions may not benefit from thrombolysis', Annals of Neurology, 80 286-293 (2016) [C1]
Objective: Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients f... [more]
Objective: Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regardless of thrombolysis administration. Methods: We used a prospectively collected cohort of acute ischemic stroke patients being assessed for treatment with IV-alteplase, who had CTP before a treatment decision. Volumetric CTP was retrospectively analyded to identify patients with a small perfusion lesion (<15ml in volume). The primary analysis was excellent 3-month outcome in patients with a small perfusion lesion who were treated with alteplase compared to those who were not treated. Results: Of 1526 patients, 366 had a perfusion lesion <15ml and were clinically eligible for alteplase (212 being treated and 154 not treated). Median acute National Institutes of Health Stroke Scale score was 8 in each group. Of the 366 patients with a small perfusion lesion, 227 (62%) were modified Rankin Scale (mRS) 0 to 1 at day 90. Alteplase-treated patients were less likely to achieve 90-day mRS 0 to 1 (57%) than untreated patients (69%; relative risk [RR] = 0.83; 95% confidence interval [CI], 0.71¿0.97; p = 0.022) and did not have different rates of mRS 0 to 2 (72% treated patients vs 77% untreated; RR, 0.93; 95% CI, 0.82¿1.95; p = 0.23). Interpretation: This large observational cohort suggests that a portion of ischemic stroke patients clinically eligible for alteplase therapy with a small perfusion lesion have a good natural history and may not benefit from treatment. Ann Neurol 2016;80:286¿293.
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Nova |
2016 |
Bivard A, Yassi N, Krishnamurthy V, Lin L, Levi C, Spratt NJ, et al., 'A comprehensive analysis of metabolic changes in the salvaged penumbra', Neuroradiology, 58 409-415 (2016) [C1]
Introduction: We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery. M... [more]
Introduction: We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery. Methods: One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5¿h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24¿h after stroke onset, including single-voxel, short-echo-time (30¿ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area. Results: The concentrations of total creatine (5.39 vs 5.85¿mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13¿mM ± 1.57, p < 0.001) were reduced in peri-infarct tissue compared to the matching contralateral region. Baseline National Institutes of Health Stroke Score was correlated with glutamate concentration in the reperfused penumbra at 24¿h (r2 = 0.167, p = 0.017). Higher total creatine was associated with better neurological outcome at 24¿h (r2 = 0.242, p = 0.004). Lower peri-infarct glutamate was a stronger predictor of worse 3-month clinical outcome (area under the curve (AUC) 0.89, p < 0.001) than DWI volume (AUC = 0.79, p < 0.001). Conclusion: Decreased glutamate, creatine, and NAA concentrations are associated with poor neurological outcome at 24¿h and greater disability at 3¿months. The significant metabolic variation in salvaged tissue may potentially explain some of the variability seen in stroke recovery despite apparently successful reperfusion.
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Nova |
2015 |
Ang TE, Bivard A, Levi C, Ma H, Hsu CY, Campbell B, et al., 'Multi-modal CT in acute stroke: Wait for a serum creatinine before giving intravenous contrast? No!', International Journal of Stroke, 10 1014-1017 (2015) [C1]
Background: Multi-modal CT (MMCT) to guide decision making for reperfusion treatment is increasingly used, but there remains a perceived risk of contrast-induced nephropathy (CIN)... [more]
Background: Multi-modal CT (MMCT) to guide decision making for reperfusion treatment is increasingly used, but there remains a perceived risk of contrast-induced nephropathy (CIN). At our center, MMCT is used empirically without waiting for serum-creatinine (sCR) or renal profiling. Aims: To determine the incidence of CIN, examine the risk factors predisposing to its development, and investigate its effects on clinical outcome in the acute stroke population. Methods: An institution-wide protocol was implemented for acute stroke presentations to have MMCT (100-150ml nonionic tri-iodinated contrast, perfusion CT and CT angiography) without waiting for serum-creatinine to minimize delays. Intravenous saline is routinely infused (80-125ml/h) for at least 24-h after MMCT. Serial creatinine levels were measured at baseline, risk period, and follow-up. Renal profiles and clinical progress were reviewed up to 90 days. Results: We analyzed 735 consecutive patients who had MMCT for the evaluation of acute ischemic or hemorrhagic stroke during the last five-years. A total of 623 patients met the inclusion criteria for analysis: 16 cases (2·6%) biochemically qualified as CIN; however, the risk period serum-creatinine for 15 of these cases was confounded by dehydration, urinary tract infection, or medications. None of the group had progression to chronic kidney disease or required dialysis. Conclusions: The incidence of CIN is low when MMCT is used routinely to assess acute stroke patients. In this population, CIN was a biochemical phenomenon that did not have clinical manifestations, cause chronic kidney disease, require dialysis, or negatively impact on 90-day mRS outcomes. Renal profiling and waiting for a baseline serum-creatinine are an unnecessary delay to emergency reperfusion treatment. International Journal of Stroke
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Nova |
2015 |
Yassi N, Campbell BCV, Moffat BA, Steward C, Churilov L, Parsons MW, et al., 'Know your tools concordance of different methods for measuring brain volume change after ischemic stroke', Neuroradiology, 57 685-695 (2015) [C1]
Introduction: Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodologica... [more]
Introduction: Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods. Methods: Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1¿week of onset and at 1 and 3¿months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements. Results: Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions. Conclusions: Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions.
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Nova |
2015 |
Bivard A, Levi C, Krishnamurthy V, McElduff P, Miteff F, Spratt NJ, et al., 'Perfusion computed tomography to assist decision making for stroke thrombolysis', Brain, 138 1919-1931 (2015) [C1]
The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aim... [more]
The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.
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Nova |
2015 |
Aviv RI, Parsons M, Bivard A, Jahromi B, Wintermark M, 'Multiphase CT angiography: A poor man's perfusion CT', Radiology, 277 922-923 (2015) [C3]
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2015 |
Yassi N, Malpas CB, Campbell BCV, Moffat B, Steward C, Parsons MW, et al., 'Contralesional thalamic surface atrophy and functional disconnection 3 months after ischemic stroke', Cerebrovascular Diseases, 39 232-241 (2015) [C1]
Background: Remote structural and functional changes have been previously described after stroke and may have an impact on clinical outcome. We aimed to use multimodal MRI to inve... [more]
Background: Remote structural and functional changes have been previously described after stroke and may have an impact on clinical outcome. We aimed to use multimodal MRI to investigate contralesional subcortical structural and functional changes 3 months after anterior circulation ischemic stroke. Methods: Fifteen patients with acute ischemic stroke had multimodal MRI imaging (including high resolution structural T1-MPRAGE and resting state fMRI) within 1 week of onset and at 1 and 3 months. Seven healthy controls of similar age group were also imaged at a single time point. Contralesional subcortical structural volume was assessed using an automated segmentation algorithm in FMRIB's Integrated Registration and Segmentation Tool (FIRST). Functional connectivity changes were assessed using the intrinsic connectivity contrast (ICC), which was calculated using the functional connectivity toolbox for correlated and anticorrelated networks (Conn). Results: Contralesional thalamic volume in the stroke patients was significantly reduced at 3 months compared to baseline (median change -2.1%, interquartile range [IQR] -3.4-0.4, p = 0.047), with the predominant areas demonstrating atrophy geometrically appearing to be the superior and inferior surface. The difference in volume between the contralesional thalamus at baseline (mean 6.41 ml, standard deviation [SD] 0.6 ml) and the mean volume of the 2 thalami in controls (mean 7.22 ml, SD 1.1 ml) was not statistically significant. The degree of longitudinal thalamic atrophy in patients was correlated with baseline stroke severity with more severe strokes being associated with a greater degree of atrophy (Spearman's rho -0.54, p = 0.037). There was no significant difference between baseline contralesional thalamic ICC in patients and control thalamic ICC. However, in patients, there was a significant linear reduction in the mean ICC of the contralesional thalamus over the imaging time points (p = 0.041), indicating reduced connectivity to the remainder of the brain. Conclusions: These findings highlight the importance of remote brain areas, such as the contralesional thalamus, in stroke recovery. Similar methods have the potential to be used in the prediction of stroke outcome or as imaging biomarkers of stroke recovery.
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Nova |
2014 |
Bivard A, Levi C, Krishnamurthy V, Hislop-Jambrich J, Salazar P, Jackson B, et al., 'Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion', JOURNAL OF NEURORADIOLOGY, 41 307-315 (2014) [C1]
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Nova |
2014 |
Bivard A, Krishnamurthy V, Stanwell P, Levi C, Spratt NJ, Davis S, Parsons M, 'Arterial Spin Labeling Versus Bolus-Tracking Perfusion in Hyperacute Stroke', Stroke, 45 127-133 (2014) [C1]
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Nova |
2014 |
Lin L, Bivard A, Levi CR, Parsons MW, 'Comparison of computed tomographic and magnetic resonance perfusion measurements in acute ischemic stroke: Back-to-back quantitative analysis', Stroke, 45 1727-1732 (2014) [C1]
Background and Purpose: Magnetic resonance perfusion (MRP) and computed tomographic perfusion (CTP) are being increasingly applied in acute stroke trials and clinical practice, ye... [more]
Background and Purpose: Magnetic resonance perfusion (MRP) and computed tomographic perfusion (CTP) are being increasingly applied in acute stroke trials and clinical practice, yet the comparability of their perfusion values is not well validated. The aim of this study was to validate the comparability of CTP and MRP measures. METHODS-: A 3-step approach was used. Step 1 was a derivation step, where we analyzed 45 patients with acute ischemic stroke who had both CTP and MRP performed within 2 hours of each other and within 9 hours of stroke onset. In this step, we derived the optimal perfusion map with the least difference between MRP and CTP. In step 2, the optimal map was validated on whole-brain perfusion data of 15 patients. Step 3 was to apply the optimal perfusion map to define cross-modality reperfusion from acute CTP to 24-hour MRP in 45 patients and, in turn, to assess how accurately this predicted 3-month clinical outcome. RESULTS-: Among 8 different perfusion maps included in this study, time to peak of the residual function (Tmax) was the only one with a nonsignificant difference between CTP and MRP in delineating perfusion defects. This was validated on whole-brain perfusion data, showing high concordance of Tmax between the 2 modalities (concordance correlation coefficient of Lin, >0.91); the best concordance was at 6 s. At T max>6 s threshold, MRP and CTP reached substantial agreement in mismatch classification (¿ >0.61). Cross-modality reperfusion calculated by Tmax>6 s strongly predicted good functional outcome at 3 months (area under the curve, 0.979; P<0.05). CONCLUSIONS-: MRP and CTP can be used interchangeably if one uses Tmax measurement. © 2014 American Heart Association, Inc.
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Nova |
2014 |
Bivard A, Krishnamurthy V, Stanwell P, Yassi N, Spratt NJ, Nilsson M, et al., 'Spectroscopy of reperfused tissue after stroke reveals heightened metabolism in patients with good clinical outcomes', JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 34 1944-1950 (2014) [C1]
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Nova |
2014 |
Bivard A, Krishnamurthy V, Levi C, McElduff P, Miteff F, Spratt N, et al., 'Stroke thrombolysis: Tissue is more important than time.', CEREBROVASCULAR DISEASES, 37 154-154 (2014)
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2014 |
Bivard A, Krishnamurthy V, Levi C, McElduff P, Miteff F, Spratt N, et al., 'Does the presence of CTP mismatch predict better outcomes in thrombolysis-treated patients?', CEREBROVASCULAR DISEASES, 37 344-344 (2014)
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2014 |
Cheng X, Cao W, Ling Y, Tin L, Parsons MP, Dong Q, Bivard A, 'Cerebral white matter hypoperfusion predisposes to small vessel stroke subtypes and haemorrhagic transformation', CEREBROVASCULAR DISEASES, 37 493-493 (2014)
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2014 |
Bivard A, Levi C, Krishnamurthy V, McElduff P, Miteff F, Spratt N, et al., 'Better stroke outcomes despite worse baseline stroke severity - the value of a combined clinical and advanced CT selection approach to thrombolysis.', CEREBROVASCULAR DISEASES, 37 701-701 (2014)
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2013 |
Bendinelli C, Bivard A, Nebauer S, Parsons MW, Balogh ZJ, 'Brain CT perfusion provides additional useful information in severe traumatic brain injury', INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED, 44 1208-1212 (2013) [C1]
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Nova |
2013 |
Bivard A, Levi C, Spratt N, Parsons M, 'Perfusion CT in Acute Stroke: A Comprehensive Analysis of Infarct and Penumbra', RADIOLOGY, 267 543-550 (2013) [C1]
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Nova |
2013 |
Yassi N, Parsons MW, Christensen S, Sharma G, Bivard A, Donnan GA, et al., 'Prediction of Poststroke Hemorrhagic Transformation Using Computed Tomography Perfusion', Stroke, 44 3039-3043 (2013) [C1]
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Nova |
2013 |
Bivard A, Lin L, Parsons MW, 'Review of Stroke Thrombolytics', JOURNAL OF STROKE, 15 90-98 (2013)
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2013 |
Menon BK, O'Brien B, Bivard A, Spratt NJ, Demchuk AM, Miteff F, et al., 'Assessment of leptomeningeal collaterals using dynamic CT angiography in patients with acute ischemic stroke', Journal of Cerebral Blood Flow and Metabolism, 33 365-371 (2013) [C1]
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Nova |
2013 |
Bivard A, Stanwell PT, Levi CR, Parsons MW, 'Arterial spin labeling identifies tissue salvage and good clinical recovery after acute ischemic stroke', Journal of Neuroimaging, 23 391-396 (2013) [C1]
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Nova |
2013 |
Lin L, Bivard A, Parsons MW, 'Perfusion Patterns of Ischemic Stroke on Computed Tomography Perfusion', JOURNAL OF STROKE, 15 164-173 (2013)
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2012 |
Parsons MW, Spratt NJ, Bivard A, Campbell B, Chung K, Miteff F, et al., 'A randomized trial of tenecteplase versus alteplase for acute ischemic stroke', New England Journal of Medicine, 366 1099-1107 (2012) [C1]
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Nova |
2012 |
Bivard A, Parsons M, 'ASPECTaSaurus (a dinosaur)?', Int J Stroke, 7 564-564 (2012) [C1]
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2011 |
Bivard A, Spratt NJ, Levi CR, Parsons MW, 'Acute stroke thrombolysis: Time to dispense with the clock and move to tissue-based decision making?', Expert Review of Cardiovascular Therapy, 9 451-461 (2011) [C1]
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Nova |
2011 |
Bivard A, Spratt NJ, Levi CR, Parsons MW, 'Perfusion computer tomography: Imaging and clinical validation in acute ischaemic stroke', Brain, 134 3408-3416 (2011) [C1]
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Nova |
2011 |
Parsons MW, Bivard A, McElduff P, Spratt NJ, Levi CR, 'Defining the extent of irreversible brain ischemia using perfusion computed tomography', Cerebrovascular Diseases, 31 238-245 (2011) [C1]
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Nova |