Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial

Stroke ◽  
2021 ◽  
Author(s):  
Shadi Yaghi ◽  
Eytan Raz ◽  
Seena Dehkharghani ◽  
Howard Riina ◽  
Ryan McTaggart ◽  
...  

Background and Purpose: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (T max ) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for T max delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. Methods: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume–baseline core infarct volume)/(T max 6 or 10 s volume–baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. Results: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%–87.7%) versus 5.3% (1.1%–14.6%) of penumbral tissue was consumed based on T max >6 s ( P <0.001). In the same comparison for T max >10 s, we saw a difference of 165.4% (interquartile range, 56.1%–479.8%) versus 25.7% (interquartile range, 3.2%–72.1%; P <0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on T max >6 s ( P =0.52) or T max >10 s ( P =0.92). Conclusions: Among extended window endovascular thrombectomy patients, T max >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the T max >6-s mismatch volume may remain viable in untreated patients at 24 hours.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eytan Raz ◽  
Seena Dehkharghani ◽  
Howard Riina ◽  
Ryan McTaggart ◽  
...  

Introduction: In patients with acute large vessel occlusion, the definition of penumbral tissue based on T max delay perfusion imaging is not well established in relation to late-window endovascular thrombectomy (EVT). In this study, we sought to evaluate penumbra consumption rates for T max delays in patients treated between 6 and 16 hours from last known normal. Methods: This is a secondary analysis of the DEFUSE-3 trial, which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6-16 hours of last known normal. The primary outcome is percentage penumbra consumption defined as (24 hour infarct volume-core infarct volume)/(Tmax volume-baseline core volume). We stratified the cohort into 4 categories (untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates. Results: We included 143 patients, of which 66 were untreated, 16 had TICI 0-2a, 46 had TICI 2b, and 15 had TICI 3. In untreated patients, a median (IQR) of 48% (21% - 85%) of penumbral tissue was consumed based on Tmax6 as opposed to 160.6% (51% - 455.2%) of penumbral tissue based on Tmax10. On the contrary, in patients achieving TICI 3 reperfusion, a median (IQR) of 5.3% (1.1% - 14.6%) of penumbral tissue was consumed based on Tmax6 and 25.7% (3.2% - 72.1%) of penumbral tissue based on Tmax10. Conclusion: Contrary to prior studies, we show that at least 75% of penumbral tissue with Tmax > 10 sec delay can be salvaged with successful reperfusion and new generation devices. In untreated patients, since infarct expansion can occur beyond 24 hours, future studies with delayed brain imaging are needed to determine the optimal T max delay threshold that defines penumbral tissue in patients with proximal anterior circulation large vessel occlusion.


2021 ◽  
Vol 50 (4) ◽  
pp. 397-404
Author(s):  
Kotaro Tatebayashi ◽  
Kazutaka Uchida ◽  
Hiroto Kageyama ◽  
Hirotoshi Imamura ◽  
Nobuyuki Ohara ◽  
...  

<b><i>Introduction:</i></b> The management and prognosis of acute ischemic stroke due to multiple large-vessel occlusion (LVO) (MLVO) are not well scrutinized. We therefore aimed to elucidate the differences in patient characteristics and prognosis of MLVO and single LVO (SLVO). <b><i>Methods:</i></b> The Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) enrolled 2,420 consecutive patients with acute LVO who were admitted within 24 h of onset. We compared patient prognosis between MLVO and SLVO in the favorable outcome, defined as a modified Rankin Scale (mRS) score ≤2, and in mortality at 90 days by adjusting for confounders. Additionally, we stratified MLVO patients into tandem occlusion and different territories, according to the occlusion site information and also examined their characteristics. <b><i>Results:</i></b> Among the 2,399 patients registered, 124 (5.2%) had MLVO. Although there was no difference between the 2 groups in terms of hypertension as a risk factor, the mean arterial pressure on admission was significantly higher in MLVO (115 vs. 107 mm Hg, <i>p</i> = 0.004). MLVO in different territories was more likely to be cardioembolic (42.1 vs. 10.4%, <i>p</i> = 0.0002), while MLVO in tandem occlusion was more likely to be atherothrombotic (39.5 vs. 81.3%, <i>p</i> &#x3c; 0.0001). Among MLVO, tandem occlusion had a significantly longer onset-to-door time than different territories (200 vs. 95 min, <i>p</i> = 0.02); accordingly, the tissue plasminogen activator administration was significantly less in tandem occlusion (22.4 vs. 47.9%, <i>p</i> = 0.003). However, interestingly, the endovascular thrombectomy (EVT) was performed significantly more in tandem occlusion (63.2 vs. 41.7%; adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1–5.0). The type of MLVO was the only and significant factor associated with EVT performance in multivariate analysis. The favorable outcomes were obtained less in MLVO than in SLVO (28.2 vs. 37.1%; aOR, 0.48; 95% CI, 0.30–0.76). The mortality rate was not significantly different between MLVO and SLVO (8.9 vs. 11.1%, <i>p</i> = 0.42). <b><i>Discussion/Conclusion:</i></b> The prognosis of MLVO was significantly worse than that of SLVO. In different territories, we might be able to consider more aggressive EVT interventions.


Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 31-39
Author(s):  
Federico Cagnazzo ◽  
Michel Piotin ◽  
Simon Escalard ◽  
Benjamin Maier ◽  
Marc Ribo ◽  
...  

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.


Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1616-1619 ◽  
Author(s):  
James Beharry ◽  
Michael J. Waters ◽  
Roy Drew ◽  
John N. Fink ◽  
Duncan Wilson ◽  
...  

Background and Purpose— Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before tenecteplase thrombolysis for acute ischemic stroke. Methods— We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results— We identified 13 patients receiving intravenous tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69–85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4–21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57–113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0–2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions— Our experience suggests intravenous thrombolysis with tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.


Neurosurgery ◽  
2019 ◽  
Vol 86 (6) ◽  
pp. 802-807 ◽  
Author(s):  
Gabor Toth ◽  
Santiago Ortega-Gutierrez ◽  
Jenny P Tsai ◽  
Russell Cerejo ◽  
Sami Al Kasab ◽  
...  

Abstract BACKGROUND Prospective evidence to support mechanical thrombectomy (MT) for mild ischemic stroke with large vessel occlusion (LVO) is lacking. There is uncertainty about using an invasive procedure in patients with mild symptoms. OBJECTIVE To evaluate the safety and feasibility of MT in patients with mild symptoms and LVO. METHODS Our single-arm prospective pilot study recruited patients with LVO and initial National Institute of Health Stroke Scale (NIHSS) &lt;6, who underwent standard MT. Primary safety endpoints were symptomatic intracerebral hemorrhage (sICH), and/or worsening NIHSS by ≥4 points. Secondary endpoints included angiographic recanalization, NIHSS change, final infarct volume, and modified Rankin score (mRS). RESULTS We enrolled 20 patients (mean age 65.6 ± 12.3 yr; 45% females). Thrombolysis in Cerebral Ischemia 2B/3 thrombectomy was achieved in 95%. No patients suffered sICH. One patient (5%) had neurologic worsening within 24 h because of underlying intracranial stenosis. No other complications or safety concerns were identified. Median NIHSS was significantly better at discharge (0.5, P = .007) and at last follow-up (0, P &lt; .001) than before treatment (3). Mean post vs preintervention infarct volumes were small without significant difference (1.2 ml, P = .434). Most patients (85%) were discharged directly home. Excellent clinical outcome (mRS 0-1) at last follow-up was seen in 95% of patients. CONCLUSION This is one of the first specifically designed prospective studies showing that MT is safe and feasible in patients with low NIHSS and LVO. Chronic underlying vasculopathy may be a challenging dilemma. We observed excellent clinical and radiographic outcomes, but randomized controlled trials are needed to demonstrate the efficacy of MT in this unique cohort.


Stroke ◽  
2020 ◽  
Vol 51 (2) ◽  
pp. 526-532 ◽  
Author(s):  
France Anne Victoire Pirson ◽  
Robert J. van Oostenbrugge ◽  
Wim H. van Zwam ◽  
Michel J.M. Remmers ◽  
Diederik W.J. Dippel ◽  
...  

Background and Purpose— Patients with acute ischemic stroke treated with endovascular thrombectomy may be treated with repeat endovascular thrombectomy (rEVT) in case of recurrent large vessel occlusion. Data on safety and efficacy of these interventions is scarce. Our aim is to report on frequency, timing, and outcome of rEVT in a large nation-wide multicenter registry. Methods— In the Netherlands, all patients with endovascular thrombectomy have been registered since 2002 (MR CLEAN Pretrial registry, MR CLEAN Trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], and MR CLEAN Registry). We retrospectively reviewed these databases for anterior circulation rEVT cases. Patient characteristics, procedural data, and functional outcome (modified Rankin Scale at 90 days) were analyzed. Results— Of 3928 patients treated between 2002 and 2017, 27 (0.7%) underwent rEVT. Median time between first and second procedure was 78 (1–1122) days; 11/27 patients were re-treated within 30 days. Cardioembolism was the most common etiology (18 patients [67%]). In 19 patients (70%), recurrent occlusion occurred ipsilateral to previous occlusion. At 90 days after rEVT procedure, 44% of the patients had achieved functional independence (modified Rankin Scale score of 0–2), and 33% had died. Adverse events were 2/27 (7.4%) intracranial hemorrhage, 1/27 (3.7%) stroke progression, and 1/27 (3.7%) pneumonia. Conclusions— In this large nationwide cohort of patients with acute ischemic stroke treated with endovascular thrombectomy, rEVT was rare. Stroke cause was mainly cardio-embolic, and most recurrent large vessel occlusions in which rEVT was performed occurred ipsilateral. Although there probably is a selection bias on repeated treatment in case of recurrent large vessel occlusion, rEVT appears safe, with similar outcome as in single-treated cases.


Stroke ◽  
2019 ◽  
Vol 50 (9) ◽  
pp. 2433-2440 ◽  
Author(s):  
Dashiell F. Young-Saver ◽  
Jeffrey Gornbein ◽  
Sidney Starkman ◽  
Jeffrey L. Saver

2021 ◽  
pp. 159101992110515
Author(s):  
Adnan H Siddiqui ◽  
Muhammad Waqas ◽  
Tommy Andersson ◽  
Jeffrey L Saver ◽  
Heinrich P Mattle ◽  
...  

Background A considerable proportion of stroke patients have unfavorable outcomes despite substantial reperfusion during mechanical thrombectomy for large vessel occlusion. This study aimed to determine predictors of unfavorable outcomes despite substantial reperfusion (modified thrombolysis in cerebral infarction score of ≥2b). Methods We conducted a post hoc analysis of Analysis of Revascularization in Ischemic Stroke With EmboTrap, a prospective, multicenter study on the efficacy of the EmboTrap revascularization device. We included patients with anterior large vessel occlusion, substantial reperfusion within three passes, and 3-month follow-up. Univariate and multivariate logistic regression analyses were performed to determine independent predictors of dependency or death (modified Rankin Score 3–6) at 90 days. Results Of the 176 patients included in the study, 124 (70.45%) achieved modified Rankin Score of 0–2 at 90 days and 52 (29.6%) had modified Rankin Score of 3–6. On univariate analysis, patient age and initial National Institutes of Health Stroke Scale score were significantly higher in the modified Rankin Score of 3–6 groups (71.4 ± 11.3 years vs. 66.0 ± 13.1 years, 0.01; 18.9 ± 4.13 vs. 14.6 ± 4.36, p < 0.01, respectively). Mean number of passes and symptomatic intracranial hemorrhage were also higher in patients with modified Rankin Score of 3–6 (2.46 ± 1.42 vs. 1.65 ± 0.9, p < 0.01; 13.5% vs. 2.4%, p = 0.008). On multivariate analysis, initial National Institutes of Health Stroke Scale score and mean number of passes and were independent predictors of modified Rankin Score of 3–6 at 90 days. Conclusion More severe initial neurologic deficit and higher number of passes in patients with substantial reperfusion were independent predictors of dependency or death. These findings highlight a reduction in the number of passes required to achieve reperfusion as a therapeutic target to improve the outcome after thrombectomy.


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