The Jrecan Device: Preclinical Data of a Novel Thrombectomy Device in Acute Thromboembolism Model of Beagle Dogs.

Objective: The aim of this study is to investigate the safety and efficiency of a Jrecan® flow restoration system, a novel thrombectomy device, in an arterial thromboembolic occlusion model of Beagle dogs. Methods: A total of 12 Beagle dogs with acute thromboembolism were randomized to receive mechanical thrombectomy with either Jrecan® flow restoration device or TrevoTM PROVUE Device (2:1). The efficacy and safety of the two devices, including recanalization rate, the presence of distal embolism, vasospasm, vessel perforation, and vessel injuries were evaluated through DSA and microscopic examination. Result: A 100% recanalization rate (mTICI 2b/3) was achieved in both groups. Endothelial and subendothelial injuries occurred in all target vessels. Focal disruption of internal elastic lamina was observed in 4 cases. The mean vessel injury score of the Jrecan® group was 1.16 ± 0.48, significantly lower than that of the TrevoTM group (1.54 ± 0.8) (P < 0.001). Conclusion: The Jrecan® and TrevoTM devices demonstrated an equally high recanalization rate in Beagle dogs with acute thromboembolism. However, histological findings revealed that the Jrecan® stent seemed to be safer than the TrevoTM device during clot retrieval, which might be related to a more appropriate radial force provided by the Jrecan® stent that resulted from its wider cell design.

Recanalization Treatment of Acute Ischemic Stroke Caused by Large-Artery Occlusion in the Elderly: A Comparative Analysis of "the Elderly" and "the Very Elderly".

OBJECTIVE: To assess whether the effectiveness and safety of recanalization therapy for acute ischemic stroke (AIS) caused by large-artery occlusion (LAO) differ between patients aged 60-79 years and patients aged ≥80 years. METHODS: We analyzed prospective data of patients with LAO (≥60 years) who underwent recanalization therapy at the Department of Vascular Neurosurgery, New Era Stroke Care and Research Institute, PLA Rocket Force Characteristic Medical Center, from November 2013 to July 2017. The data were compared between elderly patients (60-79 years) and very elderly patients (≥80 years). The effectiveness of recanalization therapy was evaluated using the 90-day modified Rankin scale (mRS) score, while safety was assessed by the rates of symptomatic intracranial hemorrhage (SICH) and mortality within 30 days. RESULTS: A total of 151 patients with AIS induced by LAO were included in this study. Seventy-three patients (48.3% [73/151]) had an overall favorable outcome (mRS score 0-2) after treatment. A higher proportion of patients in the elderly group showed a favorable outcome compared with the very elderly group (58.6% [34/58] vs. 41.6% [39/93], respectively; P = 0.046). The incidence of SICH (12.7% vs. 16.13%, respectively; P = 0.561) and mortality (10.3% vs. 7.5%, respectively; P = 0.548) within 30 days was not significantly different between the two groups. CONCLUSION: Recanalization treatment of LAO is more effective in elderly patients compared with very elderly patients, while the safety of recanalization treatment is comparable between these two groups.

Perforator preservation technologies (PPT) based on a new neuro-interventional classification in endovascular treatment of perforator involving aneurysms (piANs).

BACKGROUND: Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification. METHODS: The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed. RESULTS: Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13-50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence. CONCLUSIONS: Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.

Microglial Polarization: Novel Therapeutic Strategy against Ischemic Stroke.

Ischemic stroke, which is the second highest cause of death and the leading cause of disability, represents ~71% of all strokes globally. Some studies have found that the key elements of the pathobiology of stroke is immunity and inflammation. Microglia are the first line of defense in the nervous system. After stroke, the activated microglia become a double-edged sword, with distinct phenotypic changes to the deleterious M1 types and neuroprotective M2 types. Therefore, ways to promote microglial polarization toward M2 phenotype after stroke have become the focus of attention in recent years. In this review, we discuss the process of microglial polarization, summarize the alternation of signaling pathways and epigenetic regulation that control microglial polarization in ischemic stroke, aiming to find the potential mechanisms by which microglia can be transformed into the M2 polarized phenotype.

Factors associated with prominent vessel sign on susceptibility-weighted imaging in acute ischemic stroke.

The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) is not displayed in all cases of acute ischemia. We aimed to investigate the factors associated with the presence of PVS in stroke patients. Consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission. Associated factors for the presence of PVS were analyzed using univariate analyses and multivariable logistic regression analyses. A total of 218 patients were enrolled. The occurrence rate of PVS was 55.5%. Univariate analyses showed significant differences between PVS-positive group and PVS-negative group in age, history of coronary heart disease, baseline NIHSS scores, total cholesterol, hemoglobin, anterior circulation infarct, large vessel occlusion, and cardioembolism. Multivariable logistic regression analyses revealed that the independent factors associated with PVS were anterior circulation infarct (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.5-53.3), large vessel occlusion (OR 123.3; 95% CI 33.7-451.5), and cardioembolism (OR 5.6; 95% CI 2.1-15.3). Anterior circulation infarct, large vessel occlusion, and cardioembolism are independently associated with the presence of PVS on SWI.

Dissection-related carotid-cavernous fistula (CCF) following surgical revascularization of chronic internal carotid artery occlusion: a new subtype of CCF and proposed management.

BACKGROUND: The development of carotid-cavernous fistulas (CCFs) during surgical recanalization of chronic internal carotid artery occlusion (ICAO) may be secondary to severe ICA dissection rather than a focal tear of the cavernous ICA seen in typical traumatic CCFs. The purpose of this study is to investigate the causal relationship between the CCFs and severe ICA dissections and to characterize technical outcomes after treatment with stenting. METHODS: Five patients underwent treatment with self-expanding stents due to intraprocedural CCF and ICA dissection following surgical removal of ICAO plaque. The stents were telescopically placed via true channel of the dissection. Safety of the procedure was evaluated with 30-day stroke and death rate. Procedural success was determined by the efficacy of CCF obliteration and ICAO recanalization with angiography. RESULTS: All CCFs were associated with spiral and long segmental dissection from the cervical to cavernous ICA. After stenting, successful dissection reconstruction with TICI 3 was achieved in all patients, with complete (n = 4) or partial CCF (n = 1) obliteration. No patient had CCF syndrome, stroke, or death during follow-up of 6 to 37 months; but one patient had pulsatile tinnitus, which resolved 1 year later. Angiography at 6 to 24 months demonstrated CCF obliteration in all 5 patients and durable ICA patency in 4 patients. CONCLUSIONS: Intraprocedural CCFs with spiral and cervical-to-cavernous ICA dissection during ICAO surgery are dissection-related because of successful obliteration after stenting for dissection reconstruction. Self-expanding stenting through true channel of the dissection, serving as implanting stent-autograft, may be an optimal therapy for the atypical CCF complication from ICAO surgery.

Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke.

BACKGROUND: Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS). METHODS: This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models. RESULTS: This study included 4274 patients (median age 68 years [interquartile ranges {IQR}: 61-76]; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P < 0.001 and P < 0.001). In multivariable models adjusted for factors that confirmed in the univariate model, elevated serum levels of adiponectin were associated with a higher risk of MACCE (Quartile[Q]4 vs. Q1, Hazard ratio[HR] = 4.95 [95% confidence interval {CI}: 3.03-7.06]) and mortality (Q4 vs. Q1, HR = 5.63 [95% CI 3.15-7.99]). Adiponectin improved the prognostic value of the National Institutes of Health Stroke Scale (NIHSS) to predict MACCE (combined areas under the curve [AUC], 0.76; 95% CI 0.68-0.88; P = 0.001) and mortality (0.78[0.69-0.91]; P < 0.01). Subgroups analysis indicated that the prognostic role of adiponectin was more pronounced in women and patients with high levels of N-terminal-pro B-type natriuretic peptide(NT-pro BNP) (P < 0.001 and P < 0.001). CONCLUSIONS: Elevated serum levels of adiponectin were associated with a higher risk of MACCE and mortality independent of traditional risk factors in ischemic stroke patients.

Interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in large vessel occlusion stroke.

OBJECTIVE: To investigate the interactive effect of susceptibility-diffusion mismatch and recanalization status on clinical outcome in patients with acute ischemic stroke due to large vessel occlusion. METHODS: In this prospective study, consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission, including diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and time-of-flight magnetic resonance angiography (TOF-MRA). Patients with large vessel occlusion within the anterior circulation were recruited. Follow-up MRI was performed within 24 h after recanalization therapy (intravenous thrombolysis, endovascular therapy, or both). Multivariable logistic regression analysis was performed to estimate the interaction between SWI-DWI mismatch score and recanalization status on clinical outcome. RESULTS: A total of 90 patients were enrolled. A multiplicative interaction between SWI-DWI mismatch score and recanalization status on clinical outcome was observed (P=0.037). The interaction term "SWI-DWI mismatch score × successful recanalization" was significantly associated with favorable outcome (modified Rankin Scale score of 0-2 at 90 days; adjusted odds ratio [aOR], 2.162; 95% confidence interval [CI], 1.046-4.468). Stratified analysis showed that the likelihood of favorable outcome increased with the increase of SWI-DWI mismatch score in the successful recanalization group (OR, 2.140; 95% CI, 1.376-3.326), while there was no significant relationship between SWI-DWI mismatch score and clinical outcome in the unsuccessful recanalization group (OR, 1.212; 95% CI, 0.933-1.574). CONCLUSIONS: The effects of SWI-DWI mismatch and recanalization status on clinical outcome were realized through their interaction. In anterior circulation stroke due to large vessel occlusion, patients with both high SWI-DWI mismatch scores and successful recanalization were more likely to achieve a favorable outcome, while patients with unsuccessful recanalization, or with successful recanalization but low SWI-DWI mismatch scores, were less likely to have a good prognosis.

Outcomes of late endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion.

OBJECTIVES: The optimal treatment of symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) beyond 24 h from onset remains uncertain. We investigate the outcomes of late endovascular recanalization for symptomatic non-acute atherosclerotic ILAO. PATIENTS AND METHODS: From September 2013 to July 2018, with safety as the first principle, late endovascular recanalization for symptomatic non-acute atherosclerotic ILAO beyond 24 h from onset was attempted in 32 consecutive patients. Primary safety outcome was any stroke or death within 30 days. Primary efficacy outcome were functional independence at 90 days. RESULTS: The median time from imaging-documented occlusion to treatment was 25.5 days (interquartile range: 10.5-36.5) for all patients. Technical success in recanalization was achieved in 17 patients (53.1%, 17/32). The 30-day rate of any stroke or death was 5.9% (1/17) in the recanalized group versus 6.7% (1/15) in the failure group (P = 0.927). The rate of functional independence at 90 days (70.5%, 12/17) was increased significantly as compared with that before operation (23.5%, 4/17) in the recanalized group (P = 0.015). The rate of functional independence at 90 days (66.7%, 10/15) was not different from that before operation (66.7%,10/15) in the failure group (P = 1.00). The median score reduction in mRS from baseline at 90 days was 1.0 (interquartile range: 1.0-2.0) in the recanalized group versus 0 (interquartile range: 0.0-0.0) in the failure group (P＜0.001). CONCLUSION: For carefully selected patients with symptomatic non-acute atherosclerotic ILAO beyond 24 h from onset, late endovascular recanalization is technically feasible. The periprocedural safety of late endovascular recanalization is acceptable. Successful recanalization may effectively improve the degree of disability in such patients. However, it should be emphasized that revascularization of non-acute ILAO is a high risk procedure, which should only be performed by experienced operators with safety as the first principle.

Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke.

OBJECTIVE: To explore the association between serum retinoic acid (RA) level in patients with acute ischemic stroke (AIS) and mortality risk in the 6 months after admission. METHODS: From January 2015 through December 2016, patients admitted to 3 stroke centers in China for first-ever AIS were screened. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality in the 6 months after admission. The significance of serum RA level, NIH Stroke Scale score, and established risk factors in predicting mortality were determined. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in statistical analysis. RESULTS: Of the 1,530 patients enrolled, 325 died within 6 months of admission, with an all-cause mortality of 21.2% and CVD-related mortality of 13.1%. In multivariable analysis, RA levels were expressed as quartiles with the clinical variables. The results of the second to fourth quartiles (Q2-Q4) were compared with the first quartile (Q1); RA levels showed prognostic significance, with decreased all-cause and CVD mortality of 55% and 63%, respectively. After RA was added to the existing risk factors, all-cause mortality could be better reclassified, in association with only the NRI statistic (p = 0.005); CVD mortality could be better reclassified with significance, in association with both the IDI and NRI statistics (p < 0.01). CONCLUSIONS: Low circulating levels of RA were associated with increased risk of all-cause and CVD mortality in a cohort of patients with first-incidence AIS, indicating that RA level could be a predictor independent of established conventional risk factors.

Outcomes of Multimodality In situ Recanalization in Hybrid Operating Room (MIRHOR) for symptomatic chronic internal carotid artery occlusions.

BACKGROUND: An in situ recanalization procedure of endovascular therapy (ET) or carotid endarterectomy (CEA) has been attempted in patients with symptomatic chronic internal carotid artery occlusions (ICAOs), though the recanalization rates of both are low. OBJECTIVE: To investigate the outcomes of Multimodality In situ Recanalization for ICAOs in a Hybrid Operating Room (MIRHOR) at the same session. METHODS: Symptomatic chronic ICAOs were classified into type A or B (short occlusion with or without a tapered residual root [TRR]), and C or D (long occlusion with or without TRR), and managed in a hybrid operating room with ET, CEA, or both, as needed. Primary efficacy outcome was technical success of recanalization with Thrombolysis in Myocardial Infarction 3. Secondary efficacy outcome was any stroke or death within 30 days (primary safety outcome) plus an ipsilateral ischemic stroke after 30 days. RESULTS: Technical success was finally achieved in 35 (83.3%) of 42 consecutively enrolled patients with ICAO, which was significantly higher than 35.7% (15/42, p<0.001) from the initial ET or CEA alone. Furthermore, the success rate was in descending order: 100% (18/18) for type A and B occlusions, 75% (6/8) for type C occlusions, and 69% (11/16) for type D occlusions (p=0.017). Two secondary efficacy outcome events (5.1%) without mortality, including one (2.4%) primary safety outcome, were observed during a mean follow-up of 10.5 months. CONCLUSION: The MIRHOR for symptomatic chronic ICAOs at the same session significantly improves technical success, with low periprocedural complications and favorable clinical outcomes. The ICAO classification appears valuable in predicting technical success.

Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke.

Irisin was discovered as a PGC-1a-activated messenger of myocytes that links sedentary lifestyle, obesity, and diabetes. In this study, we investigated the short-term prognostic value of early measurement of irisin concentration in 1530 Han Chinese patients with acute ischemic stroke (AIS) from three stroke centers. The subjects were the first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Clinical information and stroke severity were collected at admission. Neurological evaluations were conducted at the 6-month follow-up. Serum levels of irisin, National Institutes of Health Stroke Scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 6 months. Multivariate analyses were performed using logistic regression models. During follow-up, a poor functional outcome was found in 588 patients (38.4%; 95% confidence interval (CI), 36.0-40.9%), and 325 patients died (21.2%; 95% CI, 19.2-23.3%). The stroke patients included in the study were divided into four groups according to irisin quartiles (first is the lowest level). Poor outcome across the irisin quartiles ranged from 54.5% (first quartile) to 21.7% (fourth quartile), and mortality rate ranged from 39.3% (first quartile) to 6.3% (fourth quartile). In a multivariate model using the first quartile (Q1) of irisin vs. Q2-Q4 together with the clinical variables, the marker displayed prognostic information and increased odds ratios of poor outcome by 58% (OR for Q1, 1.58 [95% CI, 1.12-2.43]) and mortality by 185% (OR for Q1, 2.85 [95% CI, 1.79-4.02]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict poor outcome (the area under the curve (AUC) with an increase from 0.73 to 0.75 [95% CI, 0.70-0.81]) and mortality (the AUC increased from 0.80 to 0.83 [95% CI, 0.78-0.87]). Irisin is a novel, independent prognostic marker improving currently used risk stratification of stroke patients. Further studies are needed to confirm this association, which may pave the way to new therapeutic options. Trial registration: ChiCTR-OPC- 17013501.

Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population.

BACKGROUND: Depression is a frequent mood disorder in stroke patient. Our aim was to determine irisin levels in serum and investigate their associations with post-stroke depression (PSD) in a 6-month follow-up study in Chinese patients with first-ever acute ischemic stroke (AIS). METHODS: The subjects were first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Neurological and neuropsychological evaluations were conducted at the 6-month follow-up. Serum irisin concentrations were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: During the study period, 1205 patients were included in the analysis. There were 370 patients (30.7%) classified as depression. The depression distribution across the irisin quartiles ranged between 49.8% (first quartile) and 9.9% (fourth quartile). In the patients with depression, serum irisin levels were lower compared with those in patients without depression (P < 0.001). In a multivariate model using the first (Q1) quartile of irisin vs. Q2-4 together with the clinical variables, the marker displayed predictive information and increased risk of PSD by 75% (odds ratio [OR] for Q1, 1.75 [95% confidence interval [CI], 1.15-2.65]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability; the area under the curve (AUC) increased from 0.77 to 0.81 (95% CI, 0.76-0.86). CONCLUSIONS: The data suggested that reduced serum levels of irisin were powerful biological markers of risk of developing PSD even after adjustment by variables. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options. TRIAL REGISTRATION: ChiCTR-OPC-17013501 . Retrospectively registered 23 September 2017.

Insulin resistance as estimated by homeostasis model assessment predicts incident post-stroke depression in Chinese subjects from ischemic stroke.

OBJECTIVE: Previous studies suggested that insulin resistance (IR) may be a significant causal risk factor for cardiovascular events and depression independent of other risk factors. In this prospective, we assess the value of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at admission to predict post-stroke depression (PSD) later developed at 3 months follow-up. METHODS: This prospective, multicenter cohort study was conducted from January 2015 through December 2016 in China. Clinical information and HOMA-IR was assessed at admission. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. RESULTS: In the study population, 56.6% were male and the median age was 59 years (interquartile range [IQR]: 51-69). One hundred and eighty-six patients (26.6%) showed depression at 3 months after admission and in 53 patients (28.5%) this depression was classified as severe. For each 1-unit increase of HOMA-IR, the unadjusted and adjusted risk of PSD increased by 63% (odds ratios [OR]: 1.63; 95% confidence interval [CI]:1.44-1.85; P < 0.001) and 27% (1.27; 1.13-1.39; P = 0.002). In a multivariate model using the fourth quartiles of HOMA-IR vs. quartiles 1 through 3 together with the clinical variables, the marker displayed prognostic information (PSD: OR for fourth quartile, 2.76 [95% CI, 1.66-3.73; P = 0.003]). CONCLUSIONS: The data suggests that the HOMA-IR may be of potential clinical relevance in identifying stroke patients at risk of developing depression, independent of the well-established predictors.