Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

A Rat Model of Middle Cerebral Artery Occlusion/Reperfusion without Damaging the Anatomical Structure of Cerebral Vessels.

Ischemic stroke stands as the primary cause of long-term disability and mortality among adults worldwide. Animal models of ischemic stroke have significantly contributed to our understanding of its pathological mechanisms and the development of potential treatments. Presently, there are two common methods involving filament (endovascular suture) techniques to induce animal models of cerebral ischemia. However, these methods have inherent limitations, such as reduced blood perfusion to the brain, damage to the external carotid artery system, impaired food and/or water intake, and sensory dysfunction of the face. This article introduces a new method for inducing a rat ischemic stroke model without compromising the cerebral vascular anatomy. In this study, the common carotid artery (CCA) of Sprague-Dawley rats was exposed, and an incision was made. A filament was then inserted through the incision into the internal carotid artery to occlude the middle cerebral artery. After 1.5 h of induced ischemia, the occluding filament was fully removed from both the internal carotid artery and the CCA. The incision in the CCA was subsequently sutured using 11-0 microsurgical sutures under a microscope (magnification 4x). Through the utilization of microsurgical techniques to repair the CCA, this study successfully developed a unique method to induce an ischemic stroke model in rats while preserving the anatomical integrity of cerebral blood vessels.

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion.

The middle cerebral artery occlusion reperfusion (MCAO/R) model is crucial for understanding the pathological mechanisms of stroke and for drug development.However, among the commonly used modeling methods, the Koizumi method often faces scrutiny due to its ligation of the common carotid artery (CCA) and its inability to achieve adequate reperfusion. Similarly, the Longa method has been criticized for disconnecting and ligating the external carotid artery (ECA). This study aims to introduce a modified model preparation method that preserves the integrity of the ECA, involves inserting a monofilament nylon suture through the CCA, repairing the ligated CCA incision, and maintaining reperfusion from the CCA. Reperfusion of blood flow was confirmed using laser speckle flow imaging. Evaluation methods such as the Longa scale, Modified Neurological Severity Score, triphenyltetrazolium chloride (TTC) staining, and immunofluorescence labeling of neurons demonstrated that this approach could induce stable ischemic nerve damage. This modified MCAO/R model protocol is simple and stable, providing valuable guidance for practitioners in the field of cerebral ischemia.

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

BACKGROUND: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. METHODS: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. RESULTS: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). CONCLUSIONS: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.

The use and abuse of survival analysis and Kaplan-Meier curves in surgical trials.

BACKGROUND: Survival analysis based on Cox regression and Kaplan-Meier curves, initially devised for oncology trials, have frequently been used in other contexts where fundamental statistical assumptions (such as a constant hazard ratio) are not satisfied. This is almost always the case in trials that compare surgery with medical management. METHODS: We review a trial that compared extracranial-intracranial bypass surgery (EC-IC bypass) with medical management (MM) of patients with symptomatic occlusion of the carotid or middle cerebral artery, where it was claimed that surgery was of no benefit. We discuss a hypothetical study and review other neurovascular trials which have also used survival analysis to compare results. RESULTS: The trial comparing EC-IC bypass and MM did not satisfy the fundamental proportional hazard assumption necessary for valid analyses. This was also the case for two prior EC-IC bypass trials, as well as for other landmark neurovascular studies, such as the trials comparing endarterectomy with MM for carotid stenoses, or for the trial that compared intervention and MM for unruptured brain arteriovenous malformations. While minor deviations may have little effect on large trials, it may be impossible to show the benefits of surgery when trial size is small and deviations large. CONCLUSION: Survival analyses are inappropriate in RCTs comparing surgery with conservative management, unless survival is calculated after the postoperative period. Alternative ways to compare final clinical outcomes, using for example a fixed follow-up period, should be planned for preventive surgical trials that compare intervention with conservative management.

Mechanism of microRNA regulating apoptosis after reperfusion in patients with mechanical thrombectomy.

Stroke is the second leading cause of death worldwide. Understanding of gene expression dynamics could bring new approaches in diagnostics and therapy of stroke. Small noncoding molecules termed 'microRNA' represent the most flexible network of gene expression regulators. To screen out miRNAs that are mainly regulated during reperfusion in mechanically embolized patients, and study their mechanisms of action in reperfusion injury after thrombectomy, in order to find new therapeutic targets for mechanically embolized patients. Serums from 30 patients with moderate to severe stroke after mechanical thrombectomy (MT) were collected to measure miRNA expressions. Clinical information of patients was analyze, and patients were divided into poor prognosis and good prognosis. Factors affecting prognosis was classified, and independent risk factors for poor prognosis were determined. Prognostic value of National Institutes of Health Stroke Scale (NIHSS) score on admission to patients with MT was assessed. ROC (receiver operating characteristic) curves were drawn, and Kaplan-Merier method determined whether different NIHSS scores at admission had any difference in the in-hospital survival rate of consistency index/random consistency index (CI/RI) patients treated with MT. An oxygen-glucose deprivation/reperfusion (OGD/R) cell model and an middle cerebral artery occlusion (MCAO)/reperfusion mouse model were established, in which miR-298 expression was tested. In OGD/R cells, proliferation, apoptosis, and autophagy were assessed after intervention with miR-298 and/or autophagy related gene 5 (ATG5). In MCAO mice, the infarct area was calculated, and neurological function was assessed. The relationship between miR-298 and ATG5 was explored and validated. Age, diabetes, hypertension, hemorrhage transformation, NIHSS score at admission, leukocyte, neutrophil count and neutrophil to lymphocyte ratio (NLR) level were associated with patient's prognosis. Diabetes, NIHSS score at admission, and hemorrhagic transformation were independent risk factors for predicting poor prognosis in patients treated with MT. NIHSS score on admission had a predictive value on patient's prognosis. miR-298 was upregulated in acute cerebral ischemia patients with MT (p<0.05), especially in those with poor prognosis. miR-298 was elevated in both cell and mouse models (p<0.05). Apoptosis and autophagy of cells were weakened after miR-298 knockdown, and infarction in the mouse brain tissues was reduced. ATG5 was a target of miR-298. Overexpressing ATG5 rescued miR-298-induced apoptosis and autophagy. In conclusion: regulation of miR-298 and ATG5 attenuates neuronal apoptosis and autophagy, providing a new strategy for brain injury after reperfusion in patients with MT.

Endovascular treatment in Danon disease: a case report.

BACKGROUND: Danon disease is a lysosomal storage disorder with X-linked inheritance. The classic triad is severe hypertrophic cardiomyopathy, myopathy, and intellectual disability, with different phenotypes between both genders. Ischemic stroke is an uncommon complication, mostly cardioembolic, related to intraventricular thrombus or atrial fibrillation, among others. CASE REPORT: We report the case of a 14-year-old Caucasian male patient with Danon disease who suffered from an acute ischemic stroke due to occlusion in the M1 segment of the middle cerebral artery. He underwent mechanical thrombectomy, resulting in successful revascularization with satisfactory clinical outcome. We objectified the intraventricular thrombus in the absence of arrhythmic events. CONCLUSION: To our knowledge, we report the first case of ischemic stroke related to Danon disease treated with endovascular treatment.

Innovative statistical approaches: the use of neural networks reduces the sample size in the splenectomy-MCAO mouse model.

AIM: To compare the effectiveness of artificial neural network (ANN) and traditional statistical analysis on identical data sets within the splenectomy-middle carotid artery occlusion (MCAO) mouse model. METHODS: Mice were divided into the splenectomized (SPLX) and sham-operated (SPLX-sham) group. A splenectomy was conducted 14 days before middle carotid artery occlusion (MCAO). Magnetic resonance imaging (MRI), bioluminescent imaging, neurological scoring (NS), and histological analysis, were conducted at two, four, seven, and 28 days after MCAO. Frequentist statistical analyses and ANN analysis employing a multi-layer perceptron architecture were performed to assess the probability of discriminating between SPLX and SPLX-sham mice. RESULTS: Repeated measures ANOVA showed no significant differences in body weight (F (5, 45)=0.696, P=0.629), NS (F (2.024, 18.218)=1.032, P=0.377) and brain infarct size on MRI between the SPLX and SPLX-sham groups post-MCAO (F (2, 24)=0.267, P=0.768). ANN analysis was employed to predict SPLX and SPL-sham classes. The highest accuracy in predicting SPLX class was observed when the model was trained on a data set containing all variables (0.7736±0.0234). For SPL-sham class, the highest accuracy was achieved when it was trained on a data set excluding the variable combination MR contralateral/animal mass/NS (0.9284±0.0366). CONCLUSION: This study validated the neuroprotective impact of splenectomy in an MCAO model using ANN for data analysis with a reduced animal sample size, demonstrating the potential for leveraging advanced statistical methods to minimize sample sizes in experimental biomedical research.

Stent Retriever Deployment Tracing Susceptibility Vessel Sign in the M2 Branch Predicts the Effective First-Pass Reperfusion in Thrombectomy for M1 Occlusion.

BACKGROUND AND PURPOSE: Successful first-pass reperfusion is associated with better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke, but its treatment strategies remain unclear. MATERIALS AND METHODS: We retrospectively recruited patients who underwent MT for M1 occlusion between December 2020 and May 2023 at our institution. The locations of susceptibility vessel sign (SVS) on magnetic resonance imaging were classified into M1 only, M1 to single M2 branch, or M1 to both M2 branches. Patients were included in the SVS tracing group when the stent retriever of the first pass covered the entire SVS length. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale 2b-3. Any intracranial hemorrhage detected at 24-hour postoperatively was included as a hemorrhagic complication. RESULTS: The SVS was detected in M1 only, M1 to single M2 branch, and M1 to both M2 branches in 8, 22, and 4 patients, respectively. Among the 34 patients, 27 were included in the SVS-tracing group. Successful first-pass reperfusion was significantly more frequent in the SVS-tracing group compared with the non-SVS tracing group (odds ratio, 14.4; 95% confidence interval, 2.0 - 101; P = 0.007). The procedural time was significantly reduced in the SVS tracing group (median, 29 [interquartile range, 22 - 49] minute vs. 63 [43 - 106] minute; P = 0.043). There was a trend toward less frequent hemorrhagic complications in the SVS tracing group (odds ratio, 0.17; 95% confidence interval, 0.029 - 1.0; P = 0.052). CONCLUSIONS: This study provides a thrombus imaging-based MT strategy to efficiently achieve first-pass reperfusion in M1 occlusion.

Modeling Robotic-Assisted Mechanical Thrombectomy Procedures with the CorPath GRX Robot: The Core-Flow Study.

BACKGROUND AND PURPOSE: Endovascular robotic devices may enable experienced neurointerventionalists to remotely perform endovascular thrombectomy. This study aimed to assess the feasibility, safety, and efficacy of robot-assisted endovascular thrombectomy compared with manual procedures by operators with varying levels of experience, using a 3D printed neurovascular model. MATERIALS AND METHODS: M1 MCA occlusions were simulated in a 3D printed neurovascular model, linked to a CorPath GRX robot in a biplane angiography suite. Four interventionalists performed manual endovascular thrombectomy (n = 45) and robot-assisted endovascular thrombectomy (n = 37) procedures. The outcomes included first-pass recanalization (TICI 2c-3), the number and size of generated distal emboli, and procedural length. RESULTS: A total of 82 experimental endovascular thrombectomies were conducted. A nonsignificant trend favoring the robot-assisted endovascular thrombectomy was observed in terms of final recanalization (89.2% versus manual endovascular thrombectomy, 71.1%; P = .083). There were no differences in total mean emboli count (16.54 [SD, 15.15] versus 15.16 [SD, 16.43]; P = .303). However, a higher mean count of emboli of > 1 mm was observed in the robot-assisted endovascular thrombectomy group (1.08 [SD, 1.00] versus 0.49 [SD, 0.84]; P = .001) compared with manual endovascular thrombectomy. The mean procedural length was longer in robot-assisted endovascular thrombectomy (6.43 [SD, 1.71] minutes versus 3.98 [SD, 1.84] minutes; P < .001). Among established neurointerventionalists, previous experience with robotic procedures did not influence recanalization (95.8% were considered experienced; 76.9% were considered novices; P = .225). CONCLUSIONS: In a 3D printed neurovascular model, robot-assisted endovascular thrombectomy has the potential to achieve recanalization rates comparable with those of manual endovascular thrombectomy within competitive procedural times. Optimization of the procedural setup is still required before implementation in clinical practice.

Decompressive craniectomy for patients with malignant infarction of the middle cerebral artery: A pooled analysis of two randomized controlled trials.

BACKGROUND: Decompressive craniectomy (DC) reduces mortality without increasing the risk of very severe disability among patients with life-threatening massive cerebral infarction. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. It remains uncertain whether DC improves the prognosis of patients with malignant middle cerebral artery (MCA) infarction receiving endovascular therapy. METHODS: We pooled data from two trials (DEVT and RESCUE BT studies in China) and patients with malignant MCA infarction were included to assess outcomes and heterogeneity of DC therapy effect. Patients with herniation were dichotomized into DC and conservative groups according to their treatment strategy. The primary outcome was the rate of mortality at 90 days. Secondary outcomes included disability level at 90 days as measured by the modified Rankin Scale score (mRS) and quality-of-life score. The associations of DC with clinical outcomes were performed using multivariable logistic regression. RESULTS: Of 98 patients with herniation, 37 received DC surgery and 61 received conservative treatment. The median (interquartile range) was 70 (62-76) years and 40.8% of the patients were women. The mortality rate at 90 days was 59.5% in the DC group compared with 85.2% in the conservative group (adjusted odds ratio, 0.31 [95% confidence interval (CI), 0.10-0.94]; P=0.04). There were 21.6% of patients in the DC group and 6.6% in the conservative group who had a mRS score of 4 (moderately severe disability); and 10.8% and 4.9%, respectively, had a score of 5 (severe disability). The quality-of-life score was higher in the DC group (0.00 [0.00-0.14] vs 0.00 [0.00-0.00], P=0.004), but DC treatment was not associated with better quality-of-life score in multivariable analyses (adjusted ß Coefficient, 0.02 [95% CI, -0.08-0.11]; p=0.75). CONCLUSIONS: DC was associated with decreased mortality among patients with malignant MCA infarction who received endovascular therapy. The majority of survivors remained moderately severe disability and required improvement on quality of life. CLINICAL TRIAL REGISTRATION: The DEVT trial: http://www.chictr.org. Identifier, ChiCTR-IOR-17013568. The RESCUE BT trial: URL: http://www.chictr.org. Identifier, ChiCTR-INR-17014167.

Mechanical thrombectomy for middle cerebral artery M2 occlusions.

BACKGROUND: The safety and efficacy of mechanical thrombectomy (MT) for proximal large vessel occlusion after acute ischemic stroke (AIS) have been demonstrated. Clinical investigations of endovascular approaches for treating AIS due to M2 occlusions have been ongoing. PURPOSE: To assess the outcomes of M2 occlusions according to treatment modality and anatomical division. METHODS: A total of 113 consecutive M2 occlusions treated with endovascular treatment (EVT) at our tertiary stroke center between January 2019 and December 2022 were retrospectively analyzed. Patients were divided into three groups: mechanical thrombectomy (MT); intravenous thrombolysis plus MT (IVT + MT); and IVT alone. The primary outcomes were good prognosis (mRS = 0-2) and mortality (mRS = 6) on day 90. The secondary outcome was to determine the differences in outcomes between lesions in the superior and inferior branches of M2. RESULTS: In total, 55 (48.7%) patients underwent MT. In 42 (37.2%) patients, bridging IVT was performed with MT, and IVT alone was applied in 16 (14.2%) patients. Neither the prognosis at 90 days nor the mortality rate significantly differed among the groups. The outcomes did not significantly differ between occlusions in the superior and inferior branches of M2. CONCLUSION: MT was found to be safe and effective for treating M2 occlusions in this series.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Thrombus migration in emergent M1 middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Thrombus migration (TM) is a well-established phenomenon in patients with intracranial vessel occlusion, particularly in those who receive alteplase. However, the relationship between TM, reperfusion success, and clinic-radiological outcomes is still being determined. This study aimed to describe the various outcomes in the event of TM in patients with M1 middle cerebral artery (M1 MCA) occlusion. MATERIALS AND METHODS: The study involved a retrospective analysis of patients undergoing endovascular thrombectomy (EVT) due to M1 MCA occlusion from two tertiary centers between January 2015 and December 2020. The proximal positions of thrombi were measured using a curve tool on CT or MR angiography before EVT. Subsequently, measurements were taken on angiographic imaging. Patients were grouped based on the amount of difference between the two measurements: growth (≤ - 10 mm), stability (> -10 mm and ≤ 10 mm), migration (> 10 mm), and resolution. RESULTS: A total of 463 patients (266 [57%] females, median 76 [interquartile range IQR: 65-83] years) were analyzed. Of them, 106 (22.8%) expressed any degree of TM. In multivariate ordinal regression analysis, the alteplase was significantly associated with TM (t = 2.192, p = 0.028), as was the greater interval from first imaging to angiography (t = 2.574, p = 0.010). In multivariate logistical regression analysis, the good clinical outcome measured by the modified Rankin scale (0-2) was not associated with TM status. CONCLUSIONS: Thrombus migration within the M1 MCA segment occurs in almost a quarter of patients, is associated with alteplase administration, and is mainly irrelevant to radiological and clinical outcome.

Effect of computed tomography vs. computed tomography perfusion on mechanical thrombectomy outcomes within 6 hours.

OBJECTIVES: It is unclear which selection strategy, plain CT vs. CT perfusion (CTP), is more powerful in predicting outcome after mechanical thrombectomy (MT). We aimed to compare the effect of plain CT and CTP in predicting outcome after MT within 6 h. METHODS: We conducted a prospective analysis of a retrospective cohort from our single-center study, which had occlusion of the internal carotid artery and middle cerebral artery up to the proximal M2 segment and received MT within 6 h. According to the Alberta Stroke Program Early CT Score (ASPECTS), patients were divided into a high-ASPECTS group (≥ 6) and a low ASPECTS group (< 6). Similarly, patients were divided into mismatch and no-mismatch groups according to the DEFUSE3 criteria for CTP. A good outcome was defined as a 90-day modified Rankin Scale (mRS) score of ≤ 3. Univariate and binary logistic regression analyses were used to investigate the association between different imaging modality and 90-day mRS score, and mortalities, respectively. RESULTS: The high ASPECTS group included 307 patients (89.2%). The mismatch group included 189 (54.9%) patients meeting the DEFUSE3 criterion. Compared to the low ASPECTS group, the high ASPECTS group had a good outcome (odds ratio (OR), 2.285; [95% confidence interval (CI) (1.106, 4.723)], p = 0.026) and lower mortality (OR, 0.350; [95% CI (0.163, 0.752)], p = 0.007). However, there were no significant differences in good outcomes and mortality between the mismatch and no-mismatch groups. CONCLUSIONS: Compared with plain CT, CTP does not provide additional benefits in the selection of patients suitable for MT within 6 h. CLINICAL RELEVANCE STATEMENT: CT perfusion is not superior to plain CT for the prediction of clinical outcomes when selecting patients for mechanical thrombectomy in the first 6 h. In that clinical setting, plain CT may be safe in the absence of perfusion data. KEY POINTS: • The advantage of CT perfusion (CTP) over CT in pre-mechanical thrombectomy (MT) screening has not been proven for patients with a large infarct core. • CTP is not better than plain CT in predicting good outcome following MT within 6 h. • Plain CT is sufficient for selecting patients suitable for MT within 6 h of large artery occlusion.

Mechanical Thrombectomy for Acute Cardiogenic Internal Carotid Artery Occlusion with Cross-Flow through the Communicating Artery.

AIM: To report mechanical thrombectomy (MT) for internal carotid artery (ICA) occlusion with cross-flow through the communicating artery ("with" group), and to compare it with ICA or middle cerebral artery occlusion without cross-flow ("without" group). MATERIAL AND METHODS: This study included 10 and 57 cases of the "with" and "without" groups, respectively. Cases analyzed by rapid processing of perfusion and diffusion (RAPID) since October 2020 were included. RESULTS: Puncture-to-reperfusion time was 78.5 and 39 min (p=0.0155), the National Institutes of Health Stroke Scale score at discharge was 10.5 and 4 (p=0.0166), decline from pre to post Diffusion-Weighted Image-Alberta Stroke Program Early computed tomography (CT) Score was 0.5 and 0 (p=0.0495), and the modified Rankin Scale score at 90 days was 4 and 2 (p=0.0195) in the "with" and "without" groups, respectively. Furthermore, Tmax values of > 6 s (50 cc vs. 164 cc; p=0.0277) and Tmax > 4 s/Tmax > 6 s ratio (3.23 vs. 1.55) (p=0.0074) were significantly different between the "with" and "without" groups. CONCLUSION: The "with" group may have been affected by the longer treatment time and being at high risk of distal migration of thrombus due to poor prognosis. Although the region with a Tmax of > 6 s tends to be small in patients of the "with" group, it indicates a low-perfusion state that can lead to cerebral infarction, and MT should be performed.

Prognostic variables predict clinical outcome after decompressive craniectomy: A single institute experience; A retrospective study.

Decompressive craniectomy (DC) is a well-established neurosurgical intervention in patients with high intracranial pressure who fail to respond to medical treatment. Data on predictive factors for functional outcomes in patients with DC who have malignant middle cerebral artery (MCA) infarction as opposed to intracranial hemorrhage (ICH) are scarce. Eighty-four patients who underwent DC treatment for ICH and malignant MCA infarction were examined. All patients underwent surgery in the Bahrain Salmaniya Medical Complex Neurosurgery Unit between January 2017 and June 2021. To determine whether any of these demonstrated a link to the functional outcome, radiographic factors were compared with clinical data. The postsurgical midline shift (MLS) (ICH group) showed the strongest correlation (ρ = 0.434; P = .006), as in the MCA infarction group as well (ρ = 0.46; P = .005). Further analyses using binary logistic regression with postsurgical basal cistern status and ∆ MLS, and it was observed to be statistically significant (odds ratios: 0.067, 95% CI: 0.007, 0.67; P = .021). The initial Glasgow coma scale, postsurgical MLS, basal cistern status, and ∆ are Measurable variables that can be used to predict outcomes in the groups with ICH and MCA infarction.

Prognostic value of recanalization attempts in endovascular therapy for M2 segment middle cerebral artery occlusions.

BACKGROUND: There is growing evidence suggesting efficacy of endovascular therapy for M2 occlusions of the middle cerebral artery. More than one recanalization attempt is often required to achieve successful reperfusion in M2 occlusions, associated with general concerns about the safety of multiple maneuvers in these medium vessel occlusions. AIM: The aim of this study was to investigate the association between the number of recanalization attempts and functional outcomes in M2 occlusions in comparison with large vessel occlusions (LVO). METHODS: Retrospective multicenter cohort study of patients who underwent endovascular therapy for primary M2 occlusions. Patients were enrolled in the German Stroke Registry at 1 of 25 comprehensive stroke centers between 2015 and 2021. The study cohort was subdivided into patients with unsuccessful reperfusion (mTICI 0-2a) and successful reperfusion (mTICI 2b-3) at first, second, third, fourth, or ⩾fifth recanalization attempt. Primary outcome was 90-day functional independence defined as modified Rankin Scale score of 0-2. Safety outcome was the occurrence of symptomatic intracranial hemorrhage. Internal carotid artery or M1 occlusions were defined as LVO and served as comparison group. RESULTS: A total of 1078 patients with M2 occlusion were included. Successful reperfusion was observed in 87.1% and 90-day functional independence in 51.9%. The rate of functional independence decreased gradually with increasing number of recanalization attempts (p < 0.001). In both M2 occlusions and LVO, successful reperfusion within three attempts was associated with greater odds of functional independence, while success at ⩾fourth attempt was not. Patients with ⩾4 attempts exhibited higher rates of symptomatic intracranial hemorrhage in M2 occlusions (6.5% vs 2.7%, p = 0.02) and LVO (7.2% vs 3.5%, p < 0.001). CONCLUSION: This study suggests a clinical benefit of successful reperfusion within three recanalization attempts in endovascular therapy for M2 occlusions, which was similar in LVO. Our findings reduce concerns about the risk-benefit ratio of multiple attempts in M2 medium vessel occlusions. DATA ACCESS STATEMENT: The data that support the findings of this study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03356392.