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  • Ovid Technologies (Wolters Kluwer Health)  (27)
  • Donnan, Geoffrey A.  (27)
  • 1
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    Online Resource
    A Topographic Study of the Evolution of the MR DWI/PWI Mismatch Pattern and Its Clinical Impact : A Study by the EPITHET and DEFUSE Investigators
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Stroke Vol. 42, No. 6 ( 2011-06), p. 1596-1601
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2011-06), p. 1596-1601
    Abstract: The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA). Methods— Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as “classical” or “nonclassical.” Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes. Results— We included 158 patients (median age, 74 years; median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume ( P 〈 0.001) and cortical infarct location ( P =0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns. Conclusions— Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.110.609016
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
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  • 2
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    Alteplase for Stroke With Unknown Onset Time in Chronic Kidney Disease: A Pooled Analysis of Individual Participant Data
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 11 ( 2022-11), p. 3295-3303
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 11 ( 2022-11), p. 3295-3303
    Abstract: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of 〈 60 ml/min/1.73m 2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. Results: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect ( P interaction =0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55–2.58] ). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls ( P =0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls ( P =0.539). Conclusions: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.039086
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 3
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    Subacute Ischemic Stroke Is Associated With Focal 11 C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. 5 ( 2012-05), p. 1341-1346
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 5 ( 2012-05), p. 1341-1346
    Abstract: Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at Aβ deposits, detected by N-methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. Methods— Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. Results— Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68–77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2–0.44; P =0.001) at median 10 (interquartile range, 7–14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls ( P =0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rho=0.48; 95% CI, 0.28–0.72). Conclusions— PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.111.636266
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 4
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    The Effects of Alteplase 3 to 6 Hours After Stroke in the EPITHET–DEFUSE Combined Dataset : Post Hoc Case–Control Study
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Stroke Vol. 44, No. 1 ( 2013-01), p. 87-93
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 1 ( 2013-01), p. 87-93
    Abstract: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques. Methods— The EPITHET–DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay 〉 6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures. Results— From 165 patients with adequate MR scans in the EPITHET–DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo ( P =0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P =0.003). Mortality and clinical outcomes were not different between groups. Conclusions— The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00238537
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.112.668301
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
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  • 5
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    Parental Care–Seeking Behavior and Prehospital Timelines of Care in Childhood Arterial Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. 10 ( 2016-10), p. 2638-2640
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 10 ( 2016-10), p. 2638-2640
    Abstract: Taking appropriate action in the prehospital setting is important for rapid stroke diagnosis in adults. Data are lacking for children. We aimed to describe parental care–seeking behavior and prehospital timelines of care in childhood arterial ischemic stroke. Methods— A structured questionnaire was developed, using value-focused event-driven conceptual modeling techniques, to interview parents of children presenting to the emergency department with arterial ischemic stroke from 2008 to 2014. Results— Twenty-five parents (median age 41 years, interquartile range 36–45) were interviewed. Twenty-four children were awake, and 1 child was asleep at stroke onset; 23 had sudden onset symptoms. Location at stroke onset included home (72%), school (8%), or other setting (20%). Carergivers present included parent (76%), another child (8%), teacher (4%), or alone (8%). Eighty-four percent of parents thought symptoms were serious, and 83% thought immediate action was required, but only 48% considered the possibility of stroke. Initial actions included calling an ambulance (36%), wait and see (24%), calling a general practitioner (16%) or family member (8%), and driving to the emergency department or family physician (both 8%). Median time from onset to emergency department arrival was 76 minutes (interquartile range 53–187), being shorter for ambulance-transported patients. Conclusions— Stroke recognition and care-seeking behavior are suboptimal, with less than half the parents considering stroke or calling an ambulance. Initiatives are required to educate parents about appropriate actions to facilitate time-critical interventions.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.116.014728
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 6
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    Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 3 ( 2023-03), p. 706-714
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 706-714
    Abstract: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or 〉 50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%] , adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63] ). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%] , aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06] ; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03] ; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%] , aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83] ; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.041061
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 7
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    Fatal and Nonfatal Events Within 14 days After Early, Intensive Mobilization Poststroke
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 96, No. 8 ( 2021-02-23), p. e1156-e1166
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 8 ( 2021-02-23), p. e1156-e1166
    Abstract: This tertiary analysis from A Very Early Rehabilitation Trial (AVERT) examined fatal and nonfatal serious adverse events (SAEs) at 14 days. Method AVERT was a prospective, parallel group, assessor blinded, randomized international clinical trial comparing mobility training commenced 〈 24 hours poststroke, termed very early mobilization (VEM), to usual care (UC). Primary outcome was assessed at 3 months. Patients with ischemic or hemorrhagic stroke within 24 hours of onset were included. Treatment with thrombolytics was allowed. Patients with severe premorbid disability or comorbidities were excluded. Interventions continued for 14 days or hospital discharge if less. The primary early safety outcome was fatal SAEs within 14 days. Secondary outcomes were nonfatal SAEs classified as neurologic, immobility-related, and other. Mortality influences were assessed using binary logistic regression adjusted for baseline stroke severity (NIH Stroke Scale [NIHSS] score) and age. Results A total of 2,104 participants were randomized to VEM (n = 1,054) or UC (n = 1,050) with a median age of 72 years (interquartile range [IQR] 63–80) and NIHSS 7 (IQR 4–12). By 14 days, 48 had died in VEM, 32 in UC, age and stroke severity adjusted odds ratio of 1.76 (95% confidence interval 1.06–2.92, p = 0.029). Stroke progression was more common in VEM. Exploratory subgroup analyses showed higher odds of death in intracerebral hemorrhage and 〉 80 years subgroups, but there was no significant treatment by subgroup interaction. No difference in nonfatal SAEs was found. Conclusion While the overall case fatality at 14 days poststroke was only 3.8%, mortality adjusted for age and stroke severity was increased with high dose and intensive training compared to usual care. Stroke progression was more common in VEM. Registration Australian New Zealand Clinical Trials Registry, ACTRN12606000185561. Classification of Evidence This study provides Class I evidence that very early mobilization increases mortality at 14 days poststroke.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000011106
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 8
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    Clopidogrel Plus Aspirin Versus Warfarin in Patients With Stroke and Aortic Arch Plaques
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. 5 ( 2014-05), p. 1248-1257
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 5 ( 2014-05), p. 1248-1257
    Abstract: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. Methods— This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2–3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta 〉 4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. Results— The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P =0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36–1.61; P =0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P =0.013). Time in therapeutic range (67% of the time for international normalized ratio 2–3) analysis by tertiles showed no significant differences across groups. Conclusions— Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00235248.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.113.004251
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
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  • 9
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    EPITHET : Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Stroke Vol. 42, No. 1 ( 2011-01), p. 59-64
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 1 ( 2011-01), p. 59-64
    Abstract: The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated. Methods— Patients were classified as having mismatch if perfusion-weighted imaging divided by coregistered diffusion-weighted imaging volume ratio was 〉 1.2 and total coregistered mismatch volume was ≥10 mL. The primary outcome was a comparison of infarct growth in alteplase vs placebo patients with coregistered mismatch. Results— Of 99 patients with baseline diffusion-weighted imaging and perfusion-weighted imaging, coregistration of both images was possible in 95 patients. Coregistered mismatch was present in 93% (88/95) compared to 85% (81/95) with standard volumetric mismatch. In the coregistered mismatch patients, of whom 45 received alteplase and 43 received placebo, the primary outcome measure of geometric mean infarct growth was significantly attenuated by a ratio of 0.58 with alteplase compared to placebo (1.02 vs 1.77; 95% CI, 0.33–0.99; P =0.0459). Conclusions— When using coregistration techniques to determine the presence of mismatch at study entry, alteplase significantly attenuated infarct growth. This highlights the necessity for a randomized, placebo-controlled, phase III clinical trial of alteplase using penumbral selection beyond 3 hours.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.110.580464
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
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  • 10
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    The Hidden Mismatch : An Explanation for Infarct Growth Without Perfusion-Weighted Imaging/Diffusion-Weighted Imaging Mismatch in Patients With Acute Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Stroke Vol. 42, No. 3 ( 2011-03), p. 662-668
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 3 ( 2011-03), p. 662-668
    Abstract: In ischemic stroke, MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch represents tissue at risk for infarction. Infarct growth should only take place in the presence of mismatch, although there have been reports of this occurring. We hypothesized that this observation may be attributable to the presence of undetected “hidden mismatch,” which may become obvious when coregistration techniques are used. Methods— MR PWI/DWI was performed within 48 hours of stroke onset and a final T2-weighted image at ≈3 months. Volumetric-subtraction mismatch volume was defined as PWI minus DWI volume and infarct growth was defined as T2 minus DWI volume. Coregistration mismatch volume was PWI not overlapped by DWI. Mismatch salvage was the proportion of coregistered mismatch tissue that had not progressed to infarction. Results— Thirty-four patients were studied with MR at a median of 4.9 hours (interquartile range, 2.9–21.1 hours). With the volumetric-subtraction technique, 5 patients (14.7%; 95% CI, 0.05%–0.31%) had infarct growth exceeding mismatch volume, 11 patients (32.0%) had no mismatch and, among these, 3 (27.3%) had infarct growth (median volume, 2.2 mL; interquartile range, 1.0–6.5 mL). All patients had mismatch volume identified by coregistration method that was greater than infarct growth volume. The proportion of this volume salvaged was 77.7% (interquartile range, 63.0%–98.9%). Conclusions— The illogical finding of infarct growth volume being greater than the presence of mismatch volume can be explained by the presence of “hidden mismatch,” which may be detected by coregistration methods.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.110.593236
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
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