scholarly journals The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome

2020 ◽  
Author(s):  
Rosanna Rossi ◽  
Seán Fitzgerald ◽  
Sara Molina ◽  
Oana Madalina Mereuta ◽  
Andrew Douglas ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Stroke Patients ◽  
Bridging Therapy ◽  
Clot Removal ◽  
Evidence Based Treatments ◽  
Imagej Software ◽  
Number Of Passes

Abstract Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal–Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

scholarly journals Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry

2021 ◽  
Author(s):  
Rosanna Rossi ◽  
Sara Molina ◽  
Oana Madalina Mereuta ◽  
Andrew Douglas ◽  
Seán Fitzgerald ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Bridging Therapy ◽  
Chi Squared ◽  
Blue Stain ◽  
Main Component ◽  
Imagej Software ◽  
Prior Administration

Abstract Background and purpose There is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone. Methods We collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal–Wallis tests were used for statistical analysis. Results 451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P = 0.895), FIB% (P = 0.458) and PTL% (P = 0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8–64.9) versus 36.8 (20.1–79.8) mm2, N = 1000, H1 = 7.679, P = 0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29–32.06) versus 14.97 (4.93–39.80) mm2, H1 = 3.637, P = 0.056] and significantly less fibrin [9.10 (4.62–17.98) versus 10.54 (5.57–22.48) mm2, H1 = 7.920, P = 0.005*] and platelets/other [5.04 (2.26–11.32) versus 6.54 (2.94–13.79) mm2, H1 = 9.380, P = 0.002*] than MT-alone clots. Conclusions Our results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components.

scholarly journals Treatment Efficacy Analysis in Acute Ischemic Stroke Patients Using In Silico Modeling Based on Machine Learning: A Proof-of-Principle

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1357
Author(s):  
Anthony Winder ◽  
Matthias Wilms ◽  
Jens Fiehler ◽  
Nils D. Forkert
Keyword(s):  
Machine Learning ◽  
Ischemic Stroke ◽  
Treatment Group ◽  
Acute Ischemic Stroke ◽  
In Silico ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Stroke Patients ◽  
New Devices

Interventional neuroradiology is characterized by engineering- and experience-driven device development with design improvements every few months. However, clinical validation of these new devices requires lengthy and expensive randomized controlled trials. This contribution proposes a machine learning-based in silico study design to evaluate new devices more quickly with a small sample size. Acute diffusion- and perfusion-weighted MRI, segmented one-week follow-up imaging, and clinical variables were available for 90 acute ischemic stroke patients. Three treatment option-specific random forest models were trained to predict the one-week follow-up lesion segmentation for (1) patients successfully recanalized using intra-arterial mechanical thrombectomy, (2) patients successfully recanalized using intravenous thrombolysis, and (3) non-recanalizing patients as an analogue for conservative treatment for each patient in the sample, independent of the true group membership. A repeated-measures analysis of the three predicted follow-up lesions for each patient revealed significantly larger lesions for the non-recanalizing group compared to the successful intravenous thrombolysis treatment group, which in turn showed significantly larger lesions compared to the successful mechanical thrombectomy treatment group (p < 0.001). A groupwise comparison of the true follow-up lesions for the three treatment options showed the same trend but did not reach statistical significance (p = 0.19). We conclude that the proposed machine learning-based in silico trial design leads to clinically feasible results and can support new efficacy studies by providing additional power and potential early intermediate results.

scholarly journals A novel clinical nomogram for predicting 3-month unfavorable outcomes of stroke patients treated with mechanical thrombectomy

2021 ◽  
Author(s):  
Xiao-Guang Zhang ◽  
Jia-Hui Wang ◽  
Wen-Hao Yang ◽  
Xiao-Qiong Zhu ◽  
Jie Xue ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Characteristic Curve ◽  
Treatment Strategies ◽  
Stroke Patients ◽  
Bridging Therapy ◽  
Vessel Occlusion ◽  
Discriminative Performance ◽  
Preoperative Creatinine

Abstract Background: Mechanical thrombectomy (MT) is an effective treatment for large-vessel occlusion in acute ischemic stroke, however, only some revascularized patients have a good prognosis. For stroke patients undergoing MT, predicting the risk of unfavorable outcomes and adjusting the treatment strategies accordingly can greatly improve prognosis. Therefore, we aimed to develop and validate a nomogram that can predict 3-month unfavorable outcomes for individual stroke patient treated with MT. Methods: We analyzed 238 patients with acute ischemic stroke who underwent MT from January 2018 to October 2020. The primary outcome was a 3-month unfavorable outcome, assessed using the modified Rankin Scale (mRS), 3-6. A nomogram was generated based on a multivariable logistic model. We used the area under the receiver-operating characteristic curve to evaluate the discriminative performance and used the calibration curve and Spiegelhalter’s Z-test to assess the calibration performance of the risk prediction model. Results: After multivariable logistic regression, six variables (gender, bridging therapy, postoperative mTICI, stroke-associated pneumonia, preoperative creatinine and Na) remained independent predictors of 3-month unfavorable outcomes in stroke patients treated with MT, thus forming a nomogram. The area under the nomogram curve was 0.848 with good calibration performance (P = 0.946 for the Spiegelhalter’s Z-test). Conclusions: A novel nomogram consisting of gender, bridging therapy, postoperative mTICI, stroke-associated pneumonia, preoperative creatinine and Na can predict the 3-month unfavorable outcomes in stroke patients treated with MT.

scholarly journals Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry

2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoting Ma ◽  
Shuo Li ◽  
Baixue Jia ◽  
Dapeng Mo ◽  
Ning Ma ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Propensity Score ◽  
Acute Ischemic Stroke ◽  
Propensity Score Matching ◽  
Clinical Improvement ◽  
Low Dose ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Stroke Patients

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p &gt; 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy.

scholarly journals Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A Clinical- Histological Analysis of Retrieved Thrombi

2019 ◽  
Vol 28 (6) ◽  
pp. 684-690 ◽  
Author(s):  
Li Gong ◽  
Xiaoran Zheng ◽  
Lijin Feng ◽  
Xiang Zhang ◽  
Qiong Dong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Propensity Score ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Propensity Score Matching ◽  
Histological Analysis ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Large Artery ◽  
Bridging Therapy

Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.

Rationale and design of combination of an immune modulator Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) trial

2017 ◽  
Vol 12 (8) ◽  
pp. 906-909 ◽  
Author(s):  
Sheng Zhang ◽  
Ying Zhou ◽  
Ruiting Zhang ◽  
Meixia Zhang ◽  
Bruce Campbell ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Reperfusion Injury ◽  
Mechanical Thrombectomy ◽  
Disease Onset ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Stroke Patients ◽  
Bridging Therapy ◽  
Vessel Occlusion

Rationale In acute ischemic stroke patients with large vessel occlusion, although reperfusion within 6 h after stroke onset using combined intravenous alteplase and mechanical thrombectomy (bridging therapy) can improve functional outcome, still approximately 50% patients suffer disability which may result from reperfusion injury. Proof-of-concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in acute ischemic stroke patients as a single therapy beyond 4.5 h of disease onset, or in combination with alteplase within 4.5 h of disease onset. Aim To assess whether the treatment of fingolimod combined with bridging therapy in large vessel occlusion acute ischemic stroke patients is effective and safe. Design and sample size estimates Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) study is a randomized, open-label, multiple central trial. This study includes 98 patients with anterior circulation large vessel occlusion acute ischemic stroke who are eligible for bridging therapy, providing 80% power to reject the null hypothesis that, combined with fingolimod, the bridging therapy has an at least 15% higher penumbra tissue salvage index than receiving bridging therapy alone. Study outcomes The primary outcome is the penumbra tissue salvage index. Key secondary outcomes focus on: infarct growth and extent of clinical improvement from day 1 to day 7, frequency of parenchymal hemorrhage at day 1. Discussion If the hypothesis of FAMTAIS is confirmed, combination of fingolimod with bridging therapy is effective in attenuating reperfusion injury in patients with large vessel occlusion treated with 6 h of stroke onset.

scholarly journals Intravenous Thrombolysis Before Mechanical Thrombectomy for Acute Ischemic Stroke: A Meta‐Analysis

2021 ◽  
Author(s):  
Houwei Du ◽  
Hanhan Lei ◽  
Gareth Ambler ◽  
Shuangfang Fang ◽  
Raoli He ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Intracranial Hemorrhage ◽  
Mechanical Thrombectomy ◽  
Meta Analysis ◽  
Intravenous Thrombolysis ◽  
Bridging Therapy ◽  
Randomized Controlled ◽  
Symptomatic Intracranial Hemorrhage

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta‐analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90‐day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta‐analysis of randomized controlled trial and observational data revealed similar 90‐day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90–1.19), mortality (OR, 1.03; 95% CI, 0.78–1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76–1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51–0.91; P =0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61–0.84; P <0.001). Conclusions In this meta‐analysis of patients with acute ischemic stroke, we found no significant differences in 90‐day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: 42021234664.

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