Abstract WP106: Redefined Measure of Early Neurological Improvement Shows Treatment Benefit of Intravenous Tissue Plasminogen Activator Treatment in NINDS Rt-PA Acute Stroke Trial at 24 Hours

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Shashank Agarwal ◽  
Erica Scher ◽  
Aaron Lord ◽  
Jennifer Frontera ◽  
Koto Ishida ◽  
...  

Background and Purpose: The first of the 2 NINDS Stroke Study trials did not show a significant increase in early neurological improvement (ENI), defined as NIHSS improvement by ≥ 4, with alteplase treatment. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods: We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as [(admission NIHSS score–24-hour NIHSS score)x100/admission NIHSS score] and delta NIHSS as (admission NIHSS score–24-hour NIHSS score). We compared ENI using these definitions between alteplase vs. placebo patients. We also used receiver operating characteristic (ROC) curve to determine the predictive association of ENI with excellent 3-month functional outcomes [Barthel Index (BI) score 95 – 100 and modified Rankin scale (mRS) 0-1], good 3-month functional outcome (mRS 0-2) and 3-month infarct volume. Results: There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared to the placebo group (28% vs. 15%, p = 0.045) but not median delta NIHSS (3 vs. 2, p = 0.471). ROC curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month BI (ROC percent 0.83, ROC delta 0.76, ROS admission 0.75), excellent 3-month mRS (ROC percent 0.83, ROC delta 0.74, ROS admission 0.78), and good 3-month mRS (ROC percent 0.83, ROC delta 0.76, ROS admission 0.78). Percentage change had a stronger association with 90-day infarct volume than delta NIHSS score and both delta NIHSS and percent change in NIHSS were more pronounced with faster treatment times. Conclusion: In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Shashank Agarwal ◽  
Shawna Cutting ◽  
Brian Mac Grory ◽  
Tina Burton ◽  
Mahesh Jayaraman ◽  
...  

Background and Purpose: Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. Current definitions take into account the absolute difference between the admission and 24-hour NIHSS but this difference is usually not reported as a function of the baseline NIHSS. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS (delta NIHSS) at 24 hours. Methods: Retrospective analysis of prospectively collected single center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. Delta NIHSS was defined as the difference in admission and 24-hour NIHSS. Percent change NIHSS was defined as delta NIHSS divided by the admission NIHSS. We examined delta NIHSS and percent change NIHSS in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). Results: Among 586 patients with AIS treated with alteplase with admission NIHSS, 24-hour NIHSS, and 3-month mRS available, 194 (33.1%) had a favorable outcome at 3 months. The mean age was 65 years and 59% were men. In fully adjusted models, both delta NIHSS (OR per point decrease 1.27; 95% CI, 1.19– 1.36) and percent change NIHSS (OR per 10 percent decrease 1.17; 95% CI, 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS (0.755) was greater than delta NIHSS (0.613) or admission NIHSS (0.694). Conclusion: Percentage change in NIHSS may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jeffrey Wagner ◽  
Donald Frei ◽  
Raul Nogueira ◽  
Adnan Siddiqui ◽  
Osama O Zaidat ◽  
...  

Purpose: Mechanical thrombectomy has been demonstrated to provide benefits in the treatment of acute ischemic stroke (AIS). But whether to treat AIS patients with a large infarct core remains controversial. Although it is a common practice that patients with large infarct core are not offered endovascular treatment, previous data have consistently shown a proportion of these patients may benefit from IA intervention. The purpose of this study is to identify predictors of good outcomes in an AIS cohort with a large infarct volume previously treated with mechanical thrombectomy. Hypothesis: We hypothesize that among AIS patients with a large infarct volume, younger patients (≤66 years) who present with lower NIHSS scores will show good functional outcomes (mRS 0-2) at 90 days if treated with mechanical thrombectomy. Methods: Univariable and multivariable analyses were preformed to identify factors that predict good functional outcomes in AIS patients with ASPECTS 0-5 who were treated with the Penumbra System. Five previous prospective, multicenter trials (PIVOTAL, PICS, RetroSTART, START, SEPARATOR 3D) were included in this study. Patients who presented with symptoms of AIS were analyzed for association between presenting demographics and modified Rankin scale (mRS) score at 90 days in univariate and multivariate analyses. Results: Data for 614 patients with a median age of 69 years and an NIHSS score of 18 met study criteria. Of these, the 90-day mRS 0-2 rate and mortality were, respectively, 40.23% and 25.41%. Among those with ASPECTS 0-5 (N=93), 17.20% had good functional outcome. An age of ≤66 years was significantly associated with good outcome (p<0.0001) among those with ASPECTS 0-5. Within this age group who had ASPECTS 0-5, a baseline NIHSS score of ≤ 20 (p= 0.0088) with a target vessel location at the MCA (p=0.0210) were also strong predictors of good outcome if treated by mechanical thrombectomy. Conclusion: These data demonstrate that age ≤66 years, baseline NIHSS score of ≤ 20 with a target vessel location in the MCA are important predictors of good outcomes in an AIS cohort with a large infarct core who are eligible for mechanical thrombectomy.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Xabier Urra ◽  
Helena Ariño ◽  
Sergi Amaro ◽  
Víctor Obach ◽  
Alvaro Cervera ◽  
...  

Background: Around 30% of patients with acute stroke are excluded from thrombolysis because of mild or improving symptoms, but some of these patients don’t achieve a good recovery. We compared the clinical and radiological course in a cohort of 239 patients with mild stroke treated and not treated with thrombolysis in the same institution. Methods: We studied all patients with ischemic stroke admitted within 6 hours of symptom-onset with previous mRS≤1 and mild symptoms (NIHSS≤5) at arrival or during initial evaluation. We compared the baseline characteristics, clinical course (NIHSS), radiological outcome (final DWI lesion volume), incidence of symptomatic intracranial hemorrhage (sICH) and favourable 3-month outcome (mRS≤1) of patients treated with thrombolysis (123 tPA only and 9 endovascular interventions) or not treated (n=107). Results: Treated patients had greater clinical severity at presentation and after imaging and arrived to the hospital faster than not treated patients. In a general linear model of repeated measures, their course was significantly different (p=0.03) and thrombolised patients improved more during hospitalization. Patients with significant neurological improvement (NIHSS score>1) had more severe strokes at presentation but similar outcome, and were more often treated with tPA (p<0.001). Infarct volume was significantly correlated with NIHSS score especially at day 1. Despite the differences in the initial clinical severity, final infarct volume was similar in treated and not treated patients. The rate of sICH was similar in both groups. Outcome at 3-months was associated to past history of stroke, glucose levels and deterioration during hospital stay. On multivariate analysis, thrombolysis remained associated to neurological improvement (OR 4.34;p<0.001) and was non-significantly associated to greater chances of good functional outcome at 3-months (OR 2.38;p=0.099). Conclusions: In patients with mild stroke thrombolysis was safe and was associated to better neurological course. Overall, these results suggest that patients presenting with mild symptoms do benefit from thrombolysis.


2020 ◽  
Vol 12 (9) ◽  
pp. 837-841
Author(s):  
Shashvat M Desai ◽  
Daniel A Tonetti ◽  
Andrew A Morrison ◽  
Bradley J Molyneaux ◽  
Matthew Starr ◽  
...  

BackgroundVariability in early neurological improvement after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke is well documented. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence in patients who do not experience early improvement, is essential for prognostication and rehabilitation.ObjectiveTo determine the incidence of early and delayed functional independence and identify associated predictors after EVT.MethodsA retrospective analysis of prospectively collected data on patients undergoing EVT in the setting of anterior circulation LVO was performed. Demographic, clinical, radiological, treatment, and procedural information were analyzed. Incidence and predictors of early functional independence (EFI, modified Rankin Scale (mRS) score 0–2 at discharge) and delayed functional independence (DFI, mRS score 0–2 at 90 days in non-EFI patients) were analyzed.ResultsThree hundred and fifty-five patients met the study criteria. 55% were women and mean age was 71±15. Mean National Institutes of Health Stroke Scale (NIHSS) score was 17±6 and median Alberta Stroke Program Early CT Score was 9 (8-10). EFI was observed in 21% (73) of patients. Among non-EFI patients (282), DFI was observed in 30% (85) of patients. Shorter time to treatment (p=0.03), lower 24 hours NIHSS score (p<0.001), and smaller follow-up infarct volume (p=0.003) were independent predictors of EFI. Younger age (p=0.011), lower 24 hours NIHSS score (p=0.001), and absence of parenchymal hemorrhage (PH2; p=0.039) were independent predictors of DFI.ConclusionApproximately one-fifth of patients experience EFI and one-third of non-early improvers experience DFI. Younger age, lower 24 hours NIHSS score, and absence of parenchymal hemorrhage were independent predictors of DFI among non-early improvers. Further studies are required to improve our understanding of DFI.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Omar Kass-Hout ◽  
Tareq Kass-Hout ◽  
Michael R. Frankel ◽  
Fadi Nahab ◽  
Samir R. Belagaje ◽  
...  

Background and Purpose: Time to reperfusion is an essential factor in determination of outcomes in (AIS). We sought to establish the effect of the procedural time on the clinical and radiographic outcomes of AIS patients undergoing intra-arterial therapy. Methods: Retrospective review of a prospectively collected database of endovascularly treated large vessel AIS in a large academic center. Data from all consecutive patients who underwent mechanical thrombectomy from September 2010 to July 2012 were analyzed. The variable of interest was procedural time (defined as time from groin puncture to end of procedure). Outcome measures included the rates of symptomatic intracebral hemorrhage (sICH, defined as any parenchymal hematoma e.g. PH-1/PH-2), final infarct volume, 90-day mortality, and independent functional outcomes (modified Rankin Scale, mRS 0-2) at 90 days. Results: The entire cohort included 242 patients with a mean age of 65.5+/- 14.2 and median baseline NIHSS 20. Of the patients 49.38% were females. The median ASPECTS score was 8. The mean procedure time was significantly shorter in patients with good outcome (86.73 vs. 73.13 respectively, P-value: 0.0228). However, after controlling for ASPECTS score, type of retrieval device, TICI score, volume of infarct, interval from symptoms onset to puncture, and co-morbidities, this association did not prove to be significant (P-value = 0.7101). Patients with SICH had significantly higher mean procedure time than patients without SICH (79.65 vs. 104.5 respectively; P-value: 0.0319) which remained significant when controlling to the previous factors (OR = 0.974 with a 95 % CI of (0.957, 0.991). There was no correlation between the volume of infarction and the procedure time (r = 0.10996, P-value: 0.0984). There was no association between procedure time and 90-day mortality (77.8 vs. 88.2 minutes in survivals vs. deaths respectively; P-value: 0.0958). Conclusion: Our data support an association between the risk of SICH and a longer procedure time while no definite association between procedural times and the final infarction volume or long-term functional outcomes was found after adjustment for multiple imbalances.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shashvat Desai ◽  
Amin N Aghaebrahim ◽  
James E Siegler ◽  
Andre Monteiro ◽  
Ashutosh P Jadhav ◽  
...  

Introduction: Late time window thrombectomy trials demonstrated that good functional outcomes can be achieved up to 24 hours from stroke onset in Slow Progressors (small infarct volume and large penumbral volume). In this study, we aim to investigate whether early (<6 hours) recanalization leads to superior functional outcomes compared to delayed recanalization (>6 hours) amongst patients with similar 24-hour infarct volumes post thrombectomy. Methods: We performed a retrospective analysis of a prospectively maintained LVO stroke thrombectomy database across 3 comprehensive stroke centers. Demographic, clinical, radiological, and outcomes data were analyzed. Inclusion criteria were witnessed onset anterior circulation LVO [internal carotid or middle cerebral artery M1] strokes with a good baseline mRS score (0-1) having achieved success recanalization [mTICI 2b-3] and 24-hour infarct volume of ≤10 ml on CT head or MRI. Univariate and multivariate analysis of the impact of time to recanalization on clinical outcomes was performed. Results: Of the 499 LVO strokes undergoing thrombectomy, 30% (148) met inclusion criteria. Mean age was 70 ±14 and median NIHSS score was 17 (14-21). Early recanalization (<6h) was achieved in 65% (96) of patients. Baseline demographic (age: 73 vs 74, p=0.80) and clinical characteristics (NIHSS:16.5 vs 17, p=0.52; 24-h infarct volume: 4.4 vs 4.2 ml, p=0.60) were comparable between early versus late recanalization patients. Rates of early clinical improvement (24-h NIHSS <6) (71% vs 39%, p=0.0007) and mRS 0-2 at 90 days (68% vs 48%, p=0.019) were higher in early recanalizers compared to late recanalizers. Multivariate analysis including age, NIHSS, time to recanalization, and 24-hour infarct volume identified early recanalization as an independent predictor of mRS 0-2 at 90 days (OR-2.41 95% CI 1.89-4.50). Every 1-hour increase in time to recanalization decreased the odds of 90-day mRS 0-2 by 2.2%. Conclusion: Among patients with similar 24-hour infarct volume post thrombectomy (≤10 ml), shorter time to successful recanalization is associated with significantly higher rates of early clinical improvement and mRS 0-2 at 90 days. Increased penumbral ischemic time may have an impact on outcomes post stroke thrombectomy.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
H. B Brouwers ◽  
Svetlana Lorenzano ◽  
Lyndsey H Starks ◽  
David M Greer ◽  
Steven K Feske ◽  
...  

Purpose: Hemorrhagic transformation (HT) is a common and potentially devastating complication of ischemic stroke, however its prevalence, predictors, and outcome remain unclear. Early anticoagulation is thought to be a risk factor for HT which raises the clinical question when to (re)start anticoagulation in ischemic stroke patients who have a compelling indication, such as atrial fibrillation. We conducted a prospective cohort study to address this question and to identify association of hemorrhagic transformation with outcome measures in patients with atrial fibrillation in the setting of acute ischemic stroke. Materials and Methods: We performed a prospective study which enrolled consecutive patients admitted with acute ischemic stroke presenting to a single center over a three-year period. As part of the observational study, baseline clinical data and stroke characteristics as well as 3 month functional outcome were collected. For this sub-study, we restricted the analysis to subjects diagnosed with atrial fibrillation. CT and MRI scans were reviewed by experienced readers, blinded to clinical data, to assess for hemorrhagic transformation (using ECASS 2 criteria), microbleeds and infarct volumes in both admission and follow-up scans. Clinical and outcome data were analyzed for association with hemorrhagic transformation. Results: Of 94 patients, 63 had a history of atrial fibrillation (67.0%) and 31 had newly discovered atrial fibrillation (33.0%). We identified HT in 3 of 94 baseline scans (3.2%) and 22 of 48 follow-up scans (45.8%) obtained a median of 3 days post-stroke. In-hospital initiation of either anti-platelet (n = 36; OR 0.34 [95% CI 0.10-1.16], p-value = 0.09) or anticoagulation with unfractionated intravenous heparin or low molecular weight heparin (n = 72; OR 0.25 [95% CI 0.06-1.15], p-value = 0.08) was not associated with HT. Initial NIH Stroke Scale (NIHSS) score (median 13.0 [IQR 15.0] vs. 7.0 [IQR 10.0], p-value = 0.029) and baseline infarct volume (median 17 [IQR 42.03] vs. 5 [IQR 10.95], p-value = 0.011) were significantly higher in patients with HT compared to those without. Hemorrhagic transformation was associated with a significantly higher 48-hour median NIHSS score (20 [IQR 3.0] vs. 2 [IQR 3.25], p-value = 0.007) and larger final infarct volume (81.40 [IQR 82.75] vs. 9.95 [IQR 19.73], p-value < 0.001). Finally, we found a trend towards poorer 3-month modified Rankin Scale scores in subjects with HT (OR 11.25 [95% CI 0.97-130.22], p-value = 0.05). Conclusion: In patients with atrial fibrillation, initial NIHSS score and baseline infarct volume are associated with hemorrhagic transformation in acute ischemic stroke. Early initiation of antithrombotic therapy was not associated with hemorrhagic transformation. Patients with hemorrhagic transformation were found to have a poorer short and long term outcome and larger final infarct volumes.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Dulka Manawadu ◽  
Shankranand Bodla ◽  
Laszlo Sztriha ◽  
Josef Jarosz ◽  
Lalit Kalra

Background: The role of CT perfusion (CTP) in thrombolysis decisions remains controversial and there are no studies that compare outcomes of thrombolysis in patients with or without mismatch on CT perfusion imaging. Methods: We analysed registry data between Jan 2009 and December 2010 for patients thrombolysed within 0-4.5 hours of stroke onset in whom CTP studies were performed prior to thrombolysis. The centre followed thrombolysis guidelines but patients >80 years were included. CTP was not obligatory in the treatment protocol and failure to demonstrate a mismatch was not a contraindication to thrombolysis. We retrospectively analysed data for estimated CTP mismatch of ≥ 100% according to pre-defined criteria and compared outcomes of thrombolysed patients showing perfusion mismatch with those showing no mismatch. Findings: The sample included 160 patients aged between 32-95 years of whom 63 had no mismatch and 97 had a significant mismatch. The two groups were comparable for mean age (73 v 70 years, p=0.18), sex (49% v 54% male, p=0.75), premorbid Rankin Score (mRS) 0-2 (81% v 92%, p=0.77), vascular risk factors profile, mean baseline BP (148/87 v 148/79 mm Hg, p=0.92), mean blood glucose (6.6 v 6.6 mmols/L, p=0.98) and mean National Institute of Health Stroke Scale (NIHSS) score (14.0 v 12.6,p=0.12). Patients who had mismatch prior to thrombolysis showed lower mean 24 hour NIHSS score (7.6 v 11.8, p=0.002) and greater mean 24 hour improvement in NIHSS score (5.1 v 2.0, p=0.010). A higher proportion of patients with mismatch achieved mRS 0-1 and mRS 0-2 at 3 months (36% v 18%, p= 0.012 and 51% v 32%, p=0.015 respectively) but there were no differences in symptomatic sICH rates (1.1% v 0%). Mortality (29% v 18%) and any intracranial haemorrhages (19% v 13%) were lower in mismatch patients but did not achieve significance. Regression analyses showed that PCT mismatch prior to thrombolysis was an independent predictor of both early improvement and functional outcomes at 3 months. Conclusion: Stroke patients who have perfusion mismatch on CTP imaging prior to thrombolysis within the 4.5 hour time window show better early and 3 month outcomes compared with those in whom mismatch cannot be demonstrated. Patient selection using multimodal CT may improve the effectiveness of thrombolysis.


2018 ◽  
Vol 11 (5) ◽  
pp. 450-454 ◽  
Author(s):  
Sebastien Soize ◽  
Guillaume Fabre ◽  
Matthias Gawlitza ◽  
Isabelle Serre ◽  
Serge Bakchine ◽  
...  

Background and purposeWe aimed to identify the best definition of early neurological improvement (ENI) at 2 and 24 hours after mechanical thrombectomy (MT) and determine its ability to predict a good functional outcome at 3 months.MethodsThis retrospective analysis was based on a prospectively collected registry of patients treated by MT for ischemic stroke from May 2010 to March 2017. We included patients treated with stent-retrievers with National Institute of Health Stroke Scale (NIHSS) score before treatment and at 2 and/or 24 hours after treatment and modified Rankin Score (mRS) at 3 months. Receiver operating characteristic curve analysis was performed to estimate optimal thresholds for ENI at 2 and 24 hours. The relationship between optimal ENI definitions and good outcome at 3 months (mRS 0–2) was assessed by logistic regression.ResultsThe analysis included 246 patients. At 2 hours, the optimal threshold to predict a good outcome at 3 months was improvementin the NIHSS score of >1 point (AUC 0.83,95% CI 0.77 to 0.87), with sensitivity and specificity 78.3% (62.2–85.7%) and 84.6% (77.2–90.3%), respectively, and OR 12.67 (95% CI 4.69 to 31.10, p<0.0001). At 24 hours, the optimal threshold was an improvementin the NIHSS score of >4 points (AUC 0.93, 95% CI 0.89 to 0.96), with sensitivity and specificity 93.8% (87.7–97.5%) and 83.2% (75.7–89.2%), respectively, and OR 391.32 (95% CI 44.43 to 3448.35, p<0.0001).ConclusionsENI 24 hours after thrombectomy appears to be a straightforward surrogate of long-term endpoints and may have value in future research.


2016 ◽  
Vol 9 (10) ◽  
pp. 948-951 ◽  
Author(s):  
Sami Al Kasab ◽  
Zayed Almadidy ◽  
Alejandro M Spiotta ◽  
Aquilla S Turk ◽  
M Imran Chaudry ◽  
...  

BackgroundAcute large vessel occlusion (LVO) can result from thromboemboli or underlying intracranial atherosclerotic disease (ICAD). Although the technique for revascularization differs significantly for these two lesions (simple thrombectomy for thromboemboli and balloon angioplasty and stenting for ICAD), the underlying etiology is often unknown in acute ischemic stroke (AIS).ObjectiveTo evaluate whether procedural complications, revascularization rates, and functional outcomes differ among patients with LVO from ICAD or thromboembolism.MethodsA retrospective review of thrombectomy cases from 2008 to 2015 was carried out for cases of AIS due to underlying ICAD. Thirty-six patients were identified. A chart and imaging review was performed to determine revascularization rates, periprocedural complications, and functional outcomes. Patients with ICAD and acute LVO were compared with those with underlying thromboemboli.ResultsAmong patients with ICAD and LVO, mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 12.9±8.5, revascularization (Thrombolysis In Cerebral Infarction, TICI ≥2b) was achieved in 22/34 (64.7%) patients, 11% had postprocedural intracerebral hemorrhage (PH2), and 14/33 (42.4%) had achieved a modified Rankin Scale (mRS) score of 0–2 at the 3-month follow-up. Compared with patients without underlying ICAD, there was no difference in NIHSS on presentation, or in the postprocedural complication rate. However, procedure times for ICAD were longer (98.5±59.8 vs 37.1±34.2 min), there was significant difference in successful revascularization rate between the groups (p=0.001), and a trend towards difference in functional outcome at 3 months (p=0.07).ConclusionsDespite AIS with underlying ICAD requiring a more complex, technically demanding recanalization strategy than traditional thromboembolic AIS, it appears safe, and good outcomes are obtainable.


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