Endovascular middle cerebral artery embolic stroke model: a novel approach.

A video (video 1) describing a novel murine endovascular embolic stroke model is presented. Traditional middle cerebral artery (MCA) occlusion models include a blind insertion of a monofilament string1 2 into the common or external carotid artery with the expectation to selectively occlude the MCA. However, significant mortality occurs due to subarachnoid hemorrhage and variability in stroke size, possibly related to the filament's malposition-for example, external carotid or proximal internal carotid artery (ICA). Additionally, while the string is in place, it occludes the entire extracranial ICA affecting also the collateral pial circulation. neurintsurg;14/4/413/V1F1V1Video 1 Our model includes tail artery access, which tolerates several procedures facilitating survival studies. This model uses autologous blood3 4 clot deployed directly into the MCA, resembling what occurs in clinical practice. Autologous thrombi could be lysed with IA/IV tissue plasminogen activator.In summary, we describe a novel model that resembles real practice, permits multiple catheterizations, results in reliable embolization under fluoroscopic guidance and allows therapeutic interventions not available with traditional models.

Application of Flat-Panel Volume Computed Tomography to Evaluate Cerebral Hemorrhage After Mechanical Thrombectomy of Acute Embolic Stroke of the Anterior Circulation.

OBJECTIVE: The aim of the study was to evaluate cerebral hemorrhage (CH) and contrast media leakage (CML or commonly synonymous with "contrast staining") differentiation on flat-panel volume computed tomography (FPVCT) after intra-arterial mechanical thrombectomy. METHODS: We evaluated patients with hyperattenuation on FPVCT after intra-arterial mechanical thrombectomy between 2018 and 2021 by multiple parameters on CT angiography, FPVCT, CT, and/or magnetic resonance imaging. RESULTS: The CH (n = 43) versus CML (n = 24) groups revealed: (1) regional anatomical characteristics (preserved and distorted): 7 of 43 (9.6%) and 36 of 43 (83.7%) versus 22 of 24 (91.7%) and 2 of 24 (8.3%, P < 0.001); (2) thrombus in proximal two-thirds versus distal one-thirds M1 segment of middle cerebral artery (preserved and distorted): 17 of 21 (81.0%) and 4 of 21 (19.0%) versus 5 of 11 (45.5%) and 6 of 11 (54.5%, P = 0.040); and (3) average density ratio: 1.83 ± 0.65 versus 1.35 ± 0.13 (P = 0.004). CONCLUSIONS: Contrast media leakage can be differentiated from CH by preserved regional anatomical characteristics and relatively low average density ratio on FPVCT. Patients with CML who have embolism in proximal two thirds of M1 segment are more likely to develop hyperattenuation with preserved regional anatomy.

Effect of Alteplase Use on Outcomes in Patients With Atrial Fibrillation: Analysis of the Initiation of Anticoagulation After Cardioembolic Stroke Study.

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90-day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)-related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90-day mortality. There were 1889 patients (90.6%) who had 90-day follow-up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57-3.17) but reduced risk of 90-day mortality (OR, 0.58; 95% CI, 0.39-0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90-day mortality (OR, 0.68; 95% CI, 0.45-1.04). Conclusions Alteplase reduced 90-day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Cerebral arteriosclerosis stenosis predicts poor short-term prognosis in non-valvular atrial fibrillation related cardioembolic stroke treated by reperfusion therapy.

BACKGROUND AND PURPOSE: We aimed to investigate the association between cerebral arteriosclerosis stenosis (CAS) and the short-term prognosis of non-valvular atrial fibrillation (NVAF) related cardioembolic stroke treated by reperfusion therapy. METHODS: The data of 195 consecutive NVAF related cardioembolic stroke patients were retrospectively collected. We defined poor functional outcome as a modified Rankin scale (mRS) score of > 2 at 90 days. RESULTS: Patients with CAS were more likely to be older (75.5 ± 6.8 vs. 72.5 ± 9.2 years, p = 0.001), more current smokers (35.6% vs. 24.1%, p = 0.018), with hypertension (88.1% vs. 65.6%, p < 0.001), diabetes mellitus (50.0% vs. 20.0%, p = 0.020), dyslipidemia (33.9% vs. 23.6%, p = 0.029), previous history of stroke (30.5% vs. 19.5%, p = 0.012), and congestive heart failure (32.2% vs. 22.6%, p = 0.041). Patients with CAS had higher National Institutes of Health Stroke Scale (NIHSS) (18 [13, 22] vs. 15 [9, 19], p < 0.001), and 90-day mRS scores (5 [3, 6] vs. 3[2, 5], p < 0.001). Multivariate logistic regression analysis showed that CAS (odds ratio [OR] 3.184, 95% confidence interval [CI] 1.314-7.713, p = 0.01), NIHSS score on admission (OR 1.228 [per 1 point], 95% CI 1.146-1.316, p < 0.001), congestive heart failure (OR 2.850, 95% CI 1.108-7.331, p = 0.030), and current smokers (OR 2.841, 95% CI 1.102-7.326, p = 0.031) were independent predictors of a poor functional outcome at 90 days. CONCLUSION: We should give the coexistence of CAS and NVAF related cardioembolic stroke proper attention. CAS was an independent factor for predicting the short-term prognosis of NVAF associated cardioembolic stroke patients treated by reperfusion therapy.

Combined Omic Analyzes of Cerebral Thrombi: A New Molecular Approach to Identify Cardioembolic Stroke Origin.

Background and Purpose: The diagnosis of cardioembolic stroke can be challenging for patient management in secondary stroke prevention, particularly in the case of covert paroxysmal atrial fibrillation. The molecular composition of a cerebral thrombus is related to its origin. Therefore, proteomic and metabolomic analyses of the retrieved thrombotic material should allow the identification of biomarkers or signatures to improve the etiological diagnosis of stroke. Methods: In this pilot study, the proteome and metabolome of cerebral thrombi from atherothrombotic and cardioembolic stroke patients were studied according to ASCOD phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes; D: dissection), with the highest causality grade, from the ThrombiOMIC cohort (consecutive patients with stroke recanalized by mechanical thrombectomy in an acute phase). Proteomic and metabolomic results were used separately or combined, and the obtained omic signatures were compared with classical cardioembolic stroke predictors using pairwise comparisons of the area under receiver operating characteristics. Results: Among 59 patients of the ThrombiOMIC cohort, 34 patients with stroke showed a cardioembolic phenotype and 7 had an atherothrombotic phenotype. Two thousand four hundred fifty-six proteins and 5019 molecular features of the cerebral thrombi were identified using untargeted proteomic and metabolomic approaches, respectively. Area under receiver operating characteristics to predict the cardioembolic origin of stroke were calculated using the proteomic results (0.945 [95% CI, 0.871­1]), the metabolomic results (0.836 [95% CI, 0.714­0.958]), and combined signatures (0.996 [95% CI, 0.984­1]). The diagnostic performance of the combined signatures was significantly higher than that of classical predictors such as the plasmatic BNP (B-type natriuretic peptide) level (area under receiver operating characteristics, 0.803 [95% CI, 0.629­0.976]). Conclusions: The combined proteomic and metabolomic analyses of retrieved cerebral thrombi is a very promising molecular approach to predict the cardioembolic cause of stroke and to improve secondary stroke prevention strategies.

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Risk of Paradoxical Embolism Score Validation and Atrial Fibrillation Prediction.

Background and Purpose: The Risk of Paradoxical Embolism (RoPE) score stratifies patients with stroke according to the probability of having a patent foramen ovale (PFO), which (through Bayes theorem and simple assumptions) can be used to estimate the probability that a PFO is pathogenic in a given subgroup of patients with specific features (ie, a given RoPE score value): a higher PFO prevalence corresponds to a higher probability that a PFO is pathogenic. Among alternative mechanisms in embolic stroke of undetermined source (ESUS), the actual stroke cause may be covert atrial fibrillation. We aimed to validate the RoPE score in a large ESUS population and investigate the rate of stroke recurrence and new incident atrial fibrillation during follow-up according to PFO status and RoPE score. Methods: We pooled data of consecutive patients with ESUS from 3 prospective stroke registries. We assessed RoPE score's calibration and discrimination for the presence of PFO (and consequently for the probability that it is pathogenic). Multivariate logistic regression analysis was performed to identify factors associated with PFO. Results: Among 455 patients with ESUS (median age 59 years), 184 (40%) had PFO. The RoPE score's area under the receiver operating characteristic curve was 0.75. In addition to RoPE score variables, absence of left ventricular hypertrophy, absence of atherosclerosis, and infratentorial lesions were independently associated with PFO. In patients with PFO and RoPE 7 to 10, PFO and RoPE 0 to 6, and without PFO, new incident atrial fibrillation rate was 3.1%, 20.5%, and 31.8%, respectively (log-rank test=6.28, P=0.04). Stroke recurrences in patients with likely pathogenic PFO were not statistically different from other patients. Conclusions: This multicenter study validates the RoPE score to predict the presence/absence of PFO in patients with ESUS, which strongly suggests that RoPE score is helpful in identifying patients with ESUS with pathogenic versus incidental PFOs. Left ventricular hypertrophy, atherosclerosis, and infratentorial stroke may further improve the score. Low RoPE scores were associated with more incidental atrial fibrillation during 10-year follow-up.

Efficacy and safety of mechanical thrombectomy for cardioembolic stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Several randomized clinical trials have demonstrated the safety and efficiency of mechanical thrombectomy in the management of acute ischaemic stroke caused by larger vessel occlusion. According to the trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, acute ischaemic stroke can be divided into cardioembolic stroke and non-cardioembolic stroke. Previous studies have shown that mechanical thrombectomy in cardioembolic stroke with intracranial large artery occlusion has a poor prognosis. The reason may be that the old emboli are hard, making it difficult to remove. However, recent evidence shows that mechanical thrombectomy is also effective and safe in patients with cardioembolic stroke. Therefore, the aim of this study is to evaluate the efficacy and safety of mechanical thrombectomy for cardioembolic stroke. METHODS: The electronic database, including PubMed, Cochrane Library, EMBASE, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), VIP database, and Wan-fang database, were thoroughly retrieved from inception to December 1, 2021, without language restrictions. All randomized controlled trials that evaluated the efficacy and safety of mechanical thrombectomy in the treatment of cardioembolic stroke will be included. Primary outcomes will include vascular recanalization rate and score scale. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Dichotomous variables will be reported as risk ratio or odds ratio with 95% confidence intervals and continuous variables will be summarized as mean difference or standard mean difference with 95% confidence intervals. RESULTS: This review will be to assess the efficacy and safety of mechanical thrombectomy for cardioembolic stroke. CONCLUSIONS: The results of our findings may be helpful for clinicians and health professionals to re-examine the clinical decision-making in the treatment of cardioembolic stroke, promising way for treatment of patients with cardioembolic stroke. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY2020120035.

Thrombectomy for Treatment of Acute Stroke in the COVID-19 Pandemic.

This commentary will focus on the role of thrombectomy for the treatment of embolic stroke during the 2019 novel coronavirus disease (COVID-19). We will begin with review of recently promulgated guidelines for use of thrombectomy in COVID-19-associated stroke. We will then survey the reported experience of thrombectomy applied to treatment of large-vessel occlusion (LVO) stroke in COVID-19. We will conclude by discussing unusual challenges confronted by neuro-interventionalists seeking to perform thrombectomy in COVID-19 patients with acute LVO stroke.

Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer.

BACKGROUND AND PURPOSE: We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. METHODS: Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were quantified. RESULTS: One-hundred fifty-two patients (active cancer, 19; cardioembolism, 107; large artery atherosclerosis, 26) were included. Thrombi from the active cancer group exhibited a higher fibrin/platelet composition than did those from the cardioembolism and large artery atherosclerosis groups (median, 85.7% versus 43.9% and 42.5%; P<0.001). Fibrin/platelet composition was the only independent factor (odds ratio, 1.05 [95% CI, 1.02-1.08]) in differentiating cancer-related stroke from stroke caused by cardioembolism and large artery atherosclerosis. A fibrin/platelet proportion of ≥65% accurately predicted cancer-related stroke (area under the curve, 0.84; P<0.001). CONCLUSIONS: In thrombi retrieved from patients undergoing endovascular treatment, a high fibrin/platelet composition was a probable indicator of cancer-related stroke.

Long-Term Outcomes of Acute Endovascular Thrombectomy: Tokyo/tama-Registry of Acute Endovascular Thrombectomy (TREAT).

OBJECTIVE: Mechanical thrombectomy (MT) is the recommended treatment for patients with acute ischemic stroke due to large cerebral vessel occlusion (LVO). However, few studies have investigated long-term outcomes after MT. The aim of this study was to investigate functional outcomes at long-term follow-up (1 year after MT) in patients undergoing MT for anterior circulation LVO in real-world clinical practice. METHODS: This was a retrospective and prospective observational study using data from TREAT (Tokyo/tama-Registry of Acute Endovascular Thrombectomy), a multicenter registry of MT for acute LVO in the Tokyo metropolitan area. All subjects emergently transferred and treated with MT from January 2015 to December 2018 were selected. Patients' baseline characteristics and stroke-related parameters were evaluated. The primary outcome was the modified Rankin Scale (mRS) score 1 year after MT. The secondary outcomes were risk factors for long-term good outcomes (mRS score 0-2); transfer system (stroke bypass vs. secondary transfer) was also evaluated as a potential factor associated with good long-term outcomes. RESULTS: A total of 162 cases (mean age 73.0 years, age range 30-97 years; 59.9% male) whose mRS scores at 1 year were obtained were analyzed. The median admission National Institutes of Health Stroke Scale (NIHSS) score was 17. Overall, 42.6% of the patients achieved functional independence at 1-year follow-up. Lower initial NIHSS score and mRS score 0-2 at 90 days were the independent predictors for good long-term outcomes. Stroke bypass was associated with a higher initial NIHSS score and mRS score 0 at 1 year. CONCLUSIONS: A significant number of patients experience a good long-term outcome after MT.

Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.