BL-918 Alleviates Early Brain Injury in Rats After Subarachnoid Hemorrhage by Reducing Oxidative Stress and Promoting Mitophagy Through the ULK1/PINK1/Parkin Pathway.

BACKGROUND AND PURPOSE: Oxidative stress plays a critical role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The small molecule ULK1 agonist, BL-918, demonstrated neuroprotective effects in other central nervous system diseases; however, its role in SAH has not yet been explored. This study aimed to evaluate whether BL-918 could provide neuroprotective effects in rats following SAH. METHODS: An SAH model was established in Sprague-Dawley rats using endovascular perforation. BL-918 was administered intraperitoneally after SAH, while the ULK1 inhibitor SBI was given intraperitoneally prior to SAH modeling. PINK1 siRNA was administered into the lateral ventricle before SAH induction. The neuroprotective effects and mechanisms of BL-918 were assessed through SAH grading, brain water content measurement, blood-brain barrier permeability, neurobehavioral tests, Western blot, immunofluorescence, TUNEL staining, DHE staining, and transmission electron microscopy (TEM). RESULTS: After SAH, the expression levels of p-ULK1, PINK1, Parkin, and LC3Ⅱ increased, peaking at 24 hours post-SAH. BL-918 treatment improved neurological function in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Western blot analysis revealed that BL-918 increased the expression of p-ULK1, PINK1, Parkin, LC3Ⅱ, Bcl-xl, and Bcl-2 while inhibiting the expression of Bax and Cleaved Caspase-3. Oxidative stress-related indicators showed that BL-918 alleviated oxidative stress. Immunofluorescence and TEM results demonstrated that BL-918 promoted mitophagy and preserved mitochondrial morphology. Furthermore, the positive effects of BL-918 were reversed by SBI and PINK1 siRNA, respectively. CONCLUSION: BL-918 promoted mitophagy through the ULK1/PINK1/Parkin signaling pathway, reduced oxidative stress following SAH, and improved both short-term and long-term neurological impairments. Thus, BL-918 treatment may offer a novel therapeutic approach for patients with SAH.

Peroxiredoxin-5 alleviates early brain injury after subarachnoid hemorrhage by reducing oxidative stress.

BACKGROUND AND PURPOSE: Following subarachnoid hemorrhage (SAH), excessive activation of oxidative stress and cell apoptosis plays a critical role in early brain injury (EBI). Peroxiredoxin-5 (Prdx5), predominantly expressed in neuronal mitochondria, acts as an antioxidant. However, the role of Prdx5 in EBI after SAH remains unclear. This study aims to elucidate the antioxidative stress and anti-apoptotic effects of Prdx5 in rats following SAH. METHODS: In this study, an SAH model was established in Sprague-Dawley rats using endovascular perforation. Recombinant Prdx5 (rPrdx5) was administered intranasally to upregulate Prdx5 expression after SAH in rats. Prdx5 small interfering RNA (Prdx5 siRNA) was administered prior to SAH modelling. The neuroprotective effects of Prdx5 were validated through SAH grading, brain water content, blood-brain barrier permeability, neurobehavioral tests, immunofluorescence, TUNEL staining, and Western blotting. RESULTS: The expression levels of endogenous Prdx5 significantly decreased after SAH. Treatment with rPrdx5 improved both short-term and long-term behaviour in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Measurements of oxidative stress-related indicators, including MDA, SOD, GSH-Px and GSH/GSSG, confirmed that Prdx5 can alleviate oxidative stress in rats after SAH. Western blot analysis showed that rPrdx5 significantly increased the expression of Bcl-XL and Bcl-2 and reduced the expression of Bax and Cleaved Caspase-3, thereby exerting anti-apoptotic effects. Additionally, Prdx5 siRNA reversed the neuroprotective effects of rPrdx5, exacerbated neuronal damage and blood-brain barrier permeability, and increased levels of oxidative stress and apoptosis. CONCLUSION: In conclusion, our study demonstrated that specifically upregulating the expression of Prdx5 can reduce oxidative stress and apoptosis in rats after SAH, while also improving both short-term and long-term neurological impairments. Prdx5 is primarily expressed in the mitochondria of neuronal cells and is a crucial target for reducing ROS after SAH. rPrdx5 treatment may offer a promising therapeutic approach for clinical SAH patients.

Endovascular Treatment for Ruptured Intracranial Posterior Circulation Aneurysms: Complications and Clinical Outcomes.

OBJECTIVE: To analyze the complications and long-term follow-up results of endovascular treatment for ruptured intracranial posterior circulation aneurysms and identify outcome predictors. METHODS: A total of 194 patients with ruptured intracranial posterior circulation aneurysms treated at our center between January 2014 and June 2023 were included in this retrospective analysis. Factors influencing complications during hospitalization and clinical and angiographic outcomes were analyzed. RESULTS: Complications occurred in 57 patients (29.4%) during hospitalization. The median clinical follow-up time was 46.5 (IQR 26.0-65.3) months, with favorable outcomes observed in 81.4% (158/194) and unfavorable outcomes in 18.5% (36/194) of cases, resulting in an overall mortality rate of 11.9% (23/194). The overall 1-year and 5-year complication-free survival rates were 76.4% and 70.7%, respectively. The overall 1-year and 5-year overall survival rates were 89.5% and 85.4%, respectively. Multifactorial analysis revealed that involvement of the basilar artery (p=0.032) and perioperative external ventricular drainage (p<0.001) were independent risk factors for complications during hospitalization, while advanced age (p=0.030), poor WFNS grade (p=0.003), and use of closed cell design laser cut stents (p=0.041) were independent risk factors for unfavorable outcomes during follow-up. Among the survivors, angiography follow-up was available for 139 patients, with a follow-up rate of 81.2% (139/171) and a median follow-up time of 8 months (IQR 6-12). During this period, 9 patients experienced aneurysm recanalization, and the complete occlusion rate was 85.6%. CONCLUSION: Endovascular treatment is feasible and effective for treating ruptured intracranial aneurysms; however, there are still risks of complications and unfavorable clinical outcomes. The involvement of the BA trunk increases the risk of complications, and the use of closed cell design laser cut stents is associated with unfavorable outcomes. Clinicians should be cautious to avoid the risk factors when treating ruptured posterior circulation aneurysms and strive to minimize the occurrence of complications and unfavorable clinical outcomes.

Bioinformatics Analysis Screening and Identification of Key Biomarkers and Drug Targets in Human Glioblastoma.

BACKGROUND: Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive. AIM: The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development. OBJECTIVE: The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma. METHODS: This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape. RESULTS: The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma. CONCLUSION: The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.

Microsurgical clipping versus endovascular therapy for treating patients with middle cerebral artery aneurysms presenting with neurological ischemic symptoms.

Studies comparing different treatment methods in patients with middle cerebral artery (MCA) aneurysms in different subgroups of onset symptoms are lacking. It is necessary to explore the safety and efficacy of open surgical treatment and endovascular therapy in patients with MCA aneurysms in a specific population. This study aimed to compare microsurgical clipping versus endovascular therapy regarding complication rates and outcomes in patients with MCA aneurysms presenting with neurological ischemic symptoms. This was a retrospective cohort study in which 9656 patients with intracranial aneurysms were screened between January 2014 and July 2022. Further, 130 eligible patients were enrolled. The primary outcome was the incidence of serious adverse events (SAEs) within 30 days of treatment, whereas secondary outcomes included postprocedural target vessel-related stroke, disabling stroke or death, mortality, and aneurysm occlusion rate. Among the 130 included patients, 45 were treated with endovascular therapy and 85 with microsurgical clipping. The primary outcome of the incidence of SAEs within 30 days of treatment was significantly higher in the clipping group [clipping: 23.5%(20/85) vs endovascular: 8.9%(4/45), adjusted OR:4.05, 95% CI:1.20-13.70; P = 0.024]. The incidence of any neurological complications related to the treatment was significantly higher in the clipping group [clipping:32.9%(28/85) vs endovascular:15.6%(7/45); adjusted OR:3.49, 95%CI:1.18-10.26; P = 0.023]. Postprocedural target vessel-related stroke, disabling stroke or death, mortality rate, and complete occlusion rate did not differ significantly between the two groups. Endovascular therapy seemed to be safer in treating patients with MCA aneurysms presenting with neurological ischemic symptoms compared with microsurgical clipping, with a significantly lower incidence of SAEs within 30 days of treatment and any neurological complications related to the treatment during follow-up.

Methylated MFGE8 Promotes Early Brain Injury After Subarachnoid Hemorrhage and Inhibiting Autophagy of Nerve Cell.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) is a relatively common clinical hemorrhagic stroke crisis. The important role of early brain injury (EBI) and autophagy in SAH has been increasingly recognized in recent years. This study aims to investigate the function and the undergoing mechanism of MFGE8 in EBI after SAH. METHODS: SAH model was established using C57BL/6 mice, and the SAH cell model was constructed by oxy-hemoglobin (Oxy-Hb) induced BV2 and SH-SY5Y co-culture system. Various methods were used to detect EBI and autophagy after SAH in mouse/cell lines, including mouse neurological function score, wet/dry method, HE and Evans blue staining, etc. The effect on EBI was explored after knockdown or overexpression of key genes DNMT1, MFGE8, and P2X7R. MSP was used to detect the methylation of MFGE8 promoter region, and ChIP was used to detect the binding relationship between DNMT1 and MFGE8 promoter region. RESULTS: The results showed that the activation of autophagy attenuates EBI in SAH mice. Increased level of DNMT1 and decreased level of MFGE8 were observed in brain tissues of SAH mice. Knockdown of DNMT1 or overexpression of MFGE8 attenuates EBI in mice by promoting autophagy. At the same time, we found that DNMT1 promotes methylation of MFGE8 promoter region and suppresses its protein levels. MFGE8 downregulates P2X7R levels and subsequently activates PI3k/Akt/mTOR axis, promotes autophagy, and attenuates EBI in SAH mice. CONCLUSION: DNMT1 promotes the methylation of MFGE8 promoter region and downregulates MFGE8 level; restoring MFGE8 downregulates P2X7R, and promotes autophagy by limiting the activation of PI3k/Akt/mTOR, thus exerting a protective effect on brain tissue of SAH mice. HIGHLIGHTS: • High expression of DNMT1 and P2X7R and low expression of MFGE8 were observed in SAH mice. • Activation of autophagy reduces EBI after SAH in mice. • DNMT1/MFGE8 reduces autophagy in EBI after SAH in both mouse and cell models. • DNMT1 targets the MFGE8 promoter to upregulate its methylation level. • MFGE8 inhibits P2X7R to activate PI3k/AKT/mTOR pathway and autophagy, thus inhibiting EBI after SAH.

A systematic review and meta-analysis of Comaneci/Cascade temporary neck bridging devices for the treatment of intracranial aneurysms.

Background: The temporary neck bridging devices represented by Comaneci and Cascade are a type of promising endovascular device for the treatment of intracranial bifurcation or wide-necked aneurysms. This systematic review and meta-analysis aim to assess the efficacy and safety of Comaneci/Cascade devices for the treatment of intracranial aneurysms. Methods: We performed a systematic literature search on articles in PubMed, Embase, and Web of Science that evaluated the efficacy and safety of Comaneci/Cascade devices for endovascular treatment of intracranial aneurysms, based on the Preferred Reporting Items for Systematic Reviews and Meta Analytics (PRISMA) guideline. We extracted the characteristics and treatment related information of patients included in the study, recorded the rate of technical success, procedural related complications, and angiographic outcomes. The angiographic outcome was evaluated based on Raymond Roy classification, and adequate occlusion was defined as Raymond Ray I + II. Results: Nine studies comprising 253 patients with 255 aneurysms were included. Among them, eight studies were conducted in Europe, one study was conducted in the USA. All these studies were retrospective. 206 aneurysms (80.78%) were ruptured. The vast majority of patients with ruptured aneurysms did not receive antiplatelet therapy. The rate of technical success was 97.1% (95% CI, 94.9 to 99.3%, I2 = 0%). The rate of periprocedural clinical complications was 10.9% (95% CI, 5.4 to 22.1%, I2 = 54%). The rate of complete occlusion (RR1) and adequate occlusion (RR1 + RR2) on immediate angiography after the procedure were 77.7% (95% CI, 72.7 to 83.2%, I2 = 35%) and 98% (95% CI, 95.9 to 100%, I2 = 0%) respectively. The rate of complete occlusion (RR1) and adequate occlusion (RR1 + RR2) on the last follow-up angiography were 81.2% (95% CI, 69.2 to 95.2%, I2 = 81%) and 93.7% (95% CI, 85.6 to 100%, I2 = 69%) respectively, with follow-up range from 3 to 18 months. 22/187 (11.76%) cases of aneurysms progressed during the follow-up period. 39/187 (20.86%) cases of aneurysms received additional treatment during the follow-up period. No fatal complications occurred during the treatment. Conclusion: The Comaneci/Cascade device can be used as an auxiliary treatment for intracranial aneurysms, with a good occlusion effect, but the incidence of complications still needs to be monitored.

Complications after endovascular treatment of large basilar trunk aneurysms.

BACKGROUND AND PURPOSE: Large basilar trunk aneurysms (BTAs) have a poor natural history if left untreated and always pose a significant challenge to endovascular treatment. The present study aimed to analyze the complications after endovascular treatment of large BTAs. METHODS: This was a retrospective, observational, cohort study. Between January 2015 and September 2022, 9116 patients with intracranial aneurysms came to our institution for management, of which 34 patients with 34 large (≥10 mm) BTAs were treated with endovascular treatment. Postprocedural complications, clinical, and angiographic outcomes were evaluated. RESULTS: All 34 patients (34 aneurysms) were successfully treated, of which 13 aneurysms were treated with flow diversion (FD), and 21 aneurysms were treated with stent-assisted coiling. Neurological complications occurred in 12 (35.3%) patients, with 7 (20.6%) deaths. Ischemic complications occurred in 10 (29.4%) patients, and 4 (11.8%) patients experienced hemorrhagic events. The incidences of favorable outcomes at discharge and last follow-up were 85.3% and 75.8%, respectively. The cumulative survival rates at 1 and 3 years were 86.5% and 71.4%, respectively. Unilateral vertebral artery sacrifice was associated with postprocedural complications (hazard ratio: 3.74, 95% confidence interval: 1.06-13.25, p = 0.041). The postprocedural complication rates were comparable between patients treated with FD and stent-assisted coiling (5/13, 38.5% vs. 7/21, 33.3%, p > 0.99). Angiography follow-up was available for 21 patients, and complete aneurysm occlusion was observed in 16/21 (76.2%) aneurysms. CONCLUSIONS: Endovascular treatment might be a feasible option for treating large BTAs. However, clinicians should be alerted to procedure-related complications, especially ischemic complications that cause disability or death. Unilateral vertebral artery sacrifice might be associated with postprocedural complications.

Impact of qualifying artery on the efficacy of stenting plus medical therapy versus medical therapy alone in patients with symptomatic intracranial stenosis: a post-hoc analysis of the CASSISS trial.

BACKGROUND: A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy. METHODS: This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years. RESULTS: No significant treatment allocation-by-stenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493). CONCLUSIONS: Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy.

Deliberately Staged Combined Endovascular Embolization and Subsequent Microsurgery Resection for the Treatment of Cerebral Arteriovenous Malformations.

OBJECTIVE: Complex cerebral arteriovenous malformations (AVMs) require a combined therapy of endovascular embolization and microsurgical resection to eliminate the lesion and maximize neurological protection, while a deliberate time interval might contribute to optimal clinical outcomes. The present study aimed to explore the feasibility of this paradigm. METHODS: All patients who underwent deliberately planned presurgery embolization and microsurgery resection between 2015 and 2023 were reviewed, with baseline data, postoperative complications, and follow-up outcomes recorded. The modified Rankin scale (mRS) was used to evaluate clinical outcomes, with mRS 0-2 defined as good. RESULTS: A total of 30 patients were included in the study (15 were ruptured AVMs). The median Spetzler-Martin grade of baseline AVMs was 3 (interquartile range: 2-3). The median interval between the last embolization and microsurgery was 5 days (interquartile range: 2.25-7). The complete removal rate was 100%, and the overall permanent complication rate was 16.67%. At the last follow-up, 26 patients achieved mRS 0-2, while 28 had improved or unaltered mRS. The last follow-up mRS significantly improved from baseline and discharge (P = 0.0006 and P = 0.006). The last follow-up mRS decreased by 0.65 for each additional day of time interval before the 4.4-day inflection point (ß = -0.65, P = 0.02) in the AVM ruptured cohort. CONCLUSIONS: The deliberately staged combined procedure of embolization and microsurgery might be a safe and efficacious strategy for Spetzler-Martin grade 2-5 AVMs, 4-5 days might be an appropriate staged time interval for ruptured AVMs, although further studies are needed to substantiate these findings.

Low-profile visualized intraluminal support-within-Enterprise overlapping-stent technique versus flow diversion in the treatment of intracranial vertebrobasilar trunk dissecting aneurysms.

Background: It is necessary to explore the safety and efficacy of various endovascular treatment techniques in the treatment of patients with intracranial vertebrobasilar trunk dissecting aneurysms (VBTDAs). This study sought to compare the clinical and angiographic outcomes of patients with intracranial VBTDAs following low-profile visualized intraluminal support (LVIS)-within-Enterprise overlapping-stent technique with those of flow diversion (FD). Methods: This was a retrospective, observational, cohort study. Between January 2014 and March 2022, 9,147 patients with intracranial aneurysms were screened, and 91 patients with 95 VBTDAs who underwent LVIS-within-Enterprise overlapping-stent assisted-coiling technique or FD were included in the analysis. The primary outcome was the complete occlusion rate at the last angiographic follow-up. The secondary outcomes included adequate aneurysm occlusion, in-stent stenosis/thrombosis, general neurological complications, neurological complications within 30 days after the procedure, the mortality rate, and unfavorable outcomes. Results: Among the 91 included patients, 55 were treated with LVIS-within-Enterprise overlapping-stent technique (the LE group) and 36 were treated with FD (the FD group). The angiography results at the median follow-up time of 8 months showed complete occlusion rates of 90.0% and 60.9% for the LE and FD groups, respectively, with an adjusted odds ratio of 5.79 (95% CI: 1.35-24.85; P=0.01). Adequate aneurysm occlusion (P=0.98), in-stent stenosis/thrombosis (P=0.46), general neurological complications (P=0.22), neurological complications within 30 days after the procedure (P=0.63), mortality rate (P=0.31), and unfavorable outcomes (P=0.07) at the last clinical follow-up did not differ significantly between the 2 groups. Conclusions: A significantly higher complete occlusion rate for VBTDAs was found following LVIS-within-Enterprise overlapping-stent technique as compared with FD. The 2 treatment modalities have comparable adequate occlusion rates and safety profiles.

LVIS-within-enterprise double-stent technique with coil embolization in the treatment of patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms.

Objective: This study aimed to evaluate the feasibility of the low-profile visualized intraluminal support (LVIS)-within-enterprise double-stent technique for patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms (ari-VBDAs). Methods: A total of 30 patients with ari-VBDAs who underwent reconstructive treatment using LVIS-within-enterprise double-stent technique with coil embolization between January 2014 and May 2022 were retrospectively enrolled. Patients' characteristics and clinical and imaging outcomes were reviewed. The functional outcomes were assessed using the modified Rankin scale (mRS). Results: A total of 34 ari-VBDAs were identified, including seven (20.6%) basilar artery aneurysms and 27 (79.4%) vertebral artery aneurysms. All aneurysms were successfully treated in the acute phase. In total, six (20.0%) patients experienced in-hospital serious adverse events, including two deaths (6.7%). The median clinical follow-up time of the remaining 28 patients was 20.0 (IQR, 7.3-40.8) months. The incidences of dependency or death (mRS score of 3-6) at discharge and at the last follow-up were 16.7% and 14.3%, respectively. Aneurysm rebleeding occurred in one (3.3%) patient periprocedurally. In total, three (10.0%) patients had ischemic events, one of which occurred during the periprocedural period and two occurred during follow-up. A total of two patients (6.7%) underwent ventriculoperitoneal shunt. Imaging follow-up was available for 14 patients at the median of 12.0 (IQR, 7.0-12.3) months, with a complete occlusion rate of 93.3% (14/15). In total, one patient experienced parent artery occlusion, and no aneurysm was recanalized. Conclusion: LVIS-within-enterprise double-stent technique with coil embolization for the treatment of patients with ari-VBDAs could be performed with a good safety profile and high technical success rate. The rate of complete aneurysm occlusion during follow-up seemed to be satisfactory.

Staged Carotid Artery Stenting for Prevention of Hyperperfusion-Induced Intracerebral Hemorrhage in Patients with Very High-Grade Carotid Stenosis and Poor Collateral Compensation.

OBJECTIVE: Hyperperfusion-induced intracerebral hemorrhage (HICH) is a relatively rare but potentially devastating event after carotid artery stenting (CAS). Staged angioplasty (SAP), a 2-stage form of CAS, has been shown to be effective for preventing cerebral hyperperfusion syndrome. The aim of our retrospective single-center study was to investigate the safety and efficacy of SAP to prevent HICH in patients with very severe carotid stenosis (90%-99%) and poor collateral compensation. METHODS: Between November 2011 and August 2018, 153 patients presented with severe symptomatic carotid artery stenosis ≥90%; 96 were scheduled to undergo regular CAS, and 57 were scheduled for SAP. High risk of HICH were identified based on severe stenosis degree (90%-99%) and poor collateral compensation, which were determined using digital subtraction angiography and qualitative computed tomography perfusion. Patients' clinical data, procedural details, and occurrence of HICH were compared between regular CAS and SAP groups. RESULTS: Of 57 patients scheduled for SAP, 3 were switched to regular CAS because of intraoperative dissection. The median interval between stages I and II was 8 days (IQR: 4-20 days). One patient who was switched to regular CAS experienced HICH. HICH occurred in 1 patient (1.75%; 1/57) in the SAP group and 12 patients (12.5%; 12/96) in the regular CAS group (odds ratio 0.117, 95% confidence interval 0.014-0.990, P = 0.049). Multivariate analysis showed that SAP was negatively related to cerebral hyperperfusion syndrome (odds ratio 0.117; 95% confidence interval 0.014-0.990; P = 0.049). CONCLUSIONS: SAP is an effective treatment for avoiding HICH in patients with carotid preocclusive stenosis (90%-99%) and poor collateral compensation.

Flow Diversion vs. Stent-Assisted Coiling in the Treatment of Intradural Large Vertebrobasilar Artery Aneurysms.

Objective: To compare the safety, angiographic, and long-term clinical outcomes of intradural large vertebrobasilar artery (VBA) aneurysms following flow diversion (FD) or conventional stent-assisted coiling (SAC). Methods: We performed a retrospective study of 66 consecutive patients with intradural large VBA aneurysms between 2014 and 2021 who underwent FD or SAC. Patients' characteristics, postprocedural complications, and clinical and angiographic outcome details were reviewed. Results: A total of 66 intradural large VBA aneurysms were included, including 42 (63.6%), which were treated with SAC (SAC group) and 24 (36.4%), which were treated with FD (FD group). Clinical follow-up was obtained at the median of 24.0 [interquartile range (IQR) 12.0-45.0] months, with 34 (81.0%) patients achieved the modified Rankin Scale (mRS) ≤ 2 in the SAC group and 21 (87.5%) patients in the FD group. Thirteen (19.7%) patients experienced neurological complications, of which 9 (13.6%) patients first occurred during the periprocedural phase and 4 (6.1%) patients first occurred during follow-up. The overall complication rate and periprocedural complication rate were both higher in the SAC group, but did not reach statistical significance (23.8 vs. 12.5%, P = 0.430; 16.7 vs. 8.3%, P = 0.564). The mortality rates were similar between the groups (11.9 vs. 12.5%). Angiographic follow-up was available for 46 patients at the median of 7 (IQR 6-14) months, with a numerically higher complete occlusion rate in the SAC group (82.1 vs. 55.6%, P = 0.051) and similar adequate aneurysm occlusion rates between the groups (85.7 vs. 83.3%, P = 1.000). In the multivariate analysis, ischemic onset (P = 0.019), unilateral vertebral artery sacrifice (P = 0.008), and older age (≥60 years) (P = 0.031) were significantly associated with complications. Conclusion: There was a trend toward lower complication rate and lower complete occlusion rate for intradural large VBA aneurysms following FD as compared to SAC. FD and SAC have comparable mortality rates and favorable outcomes. Ischemic onset, unilateral vertebral artery sacrifice, and older age could increase the risk of complications.

Anterior Circulation Fusiform Aneurysms Have a Lower Occlusion Rate After Pipeline Embolization Device Treatment Than Posterior Circulation Fusiform Aneurysms: A Multicenter Cohort Study.

Objective: Intracranial fusiform aneurysms are uncommon and can occur in vessels of the anterior circulation (AC) or posterior circulation (PC). While flow diversion is one treatment option, research into Pipeline Embolization Device (PED) treatment is lacking. This study explored the efficacy and safety of PED treatment for intracranial fusiform aneurysms, and compared therapeutic effects between AC and PC aneurysms. Methods: In the post-market multi-center cohort study of embolization of intracranial aneurysms with PED in China (PLUS) registry study, we retrospectively analyzed 71 fusiform aneurysms in 67 patients among 1,171 patients treated with a PED from November 2014 to October 2019. The general characteristics, perioperative status, aneurysm occlusion rate at the last follow-up angiography, and changes in modified Rankin Scale scores were analyzed. Aneurysms were divided into AC and PC groups, and univariate and multivariate analyses were conducted. Results: The study included 26 AC (25 patients) and 45 PC (42 patients) aneurysms. A total of 75 PEDs were used, an average of 1.1 PEDs were used, and the median follow-up was 6.7 months. Fifty aneurysms (71.4%) were occluded and twenty (28.5%) were incompletely occluded. There were significantly more occluded aneurysms in the PC group than in the AC group (12 vs. 38; P = 0.001). Risk factors for incomplete occlusion were AC aneurysms (P = 0.001) and a perforating artery originating from the aneurysm (P = 0.006). The mean modified Rankin Scale score was significantly lower at the last follow up than preoperatively (0.58 vs. 0.21; P = 0.0001). Conclusion: Non-overlapping PED is a safe and effective treatment for both AC and PC fusiform aneurysms. The occlusion rate of AC fusiform aneurysms is lower than that of PC.

Endovascular Treatment of Acute Ischemic Stroke Due to Isolated Proximal Posterior Artery Occlusion.

Background: Acute ischemic stroke (AIS) due to isolated proximal posterior cerebral artery (PPCA) occlusion is rare but associated with high morbidity and mortality rates. However, the optimal treatment strategy for patients with AIS caused by PPCA remains unclear. We discuss our single-center experience with endovascular treatment (EVT) in patients with PPCA. Methods: Data from patients with AIS due to PPCA occlusion were retrospectively analyzed. We analyzed procedural details, the degree of reperfusion, functional outcomes, and complications. Functional outcomes were determined using the modified Rankin Scale (mRS) at 90 days, and good outcome was defined as mRS 0-2 at 90 days. Successful reperfusion was defined as modified treatment in cerebral ischemia (mTICI) 2b-3 after endovascular therapy. Safety variables included symptomatic hemorrhage (defined as an increase of four or more points in the National Institute of Health Stroke Scale score), vessel perforation or dissection, and new ischemic stroke in different territories. Results: Seven patients were included in this study. The mean age of the patients was 64 ± 12.4 years. Successful reperfusion was achieved in all seven patients (100%). Good outcomes were achieved at 90 days in 2 patients (28.6%), and favorable outcomes were observed in five patients (71.4%). One patient underwent angioplasty as rescue therapy after three attempts. One patient died because of severe gastrointestinal bleeding 24 h after EVT, which was probably a complication of intravenous alteplase. One patient had an embolism in the basilar artery and achieved complete reperfusion after rescue thrombectomy. Another patient had a complication of vessel dissection in the PPCA and underwent stent implantation as rescue therapy. We observed no recurrence of ischemic stroke or any intracranial hemorrhage on non-contrast computed tomography 24 h after the procedure. Conclusion: EVT may represent an alternative treatment strategy for patients with acute ischemic stroke caused by PPCA.

Incomplete occlusion and visual symptoms of peri-ophthalmic aneurysm after treatment with a pipeline embolization device: a multi-center cohort study.

OBJECTIVE: Peri-ophthalmic aneurysm is a special type of aneurysm. We assessed the relationship between ophthalmic artery (OA) origin and aneurysm and examined the effect of a pipeline embolization device (PED, Covidien/Medtronic) with or without coils on aneurysm occlusion rate and visual outcomes. METHODS: We retrospectively analyzed 194 peri-ophthalmic aneurysms in 189 patients among 1171 patients treated with a PED in a Chinese post-market multi-center registry study from November 2014 to October 2019. Peri-ophthalmic aneurysms were defined as carotid-ophthalmic segment aneurysms arising from the internal carotid artery dorsal wall at, or distal to, the OA origin, with a superior or superomedial projection. The relationship between OA origin and the aneurysm was classified as follows: type A, OA originating separate from the aneurysm; type B, OA originating from the aneurysm neck or dome. Patients with aneurysm were divided into the PED-only group and the PED + coils group according to treatment. RESULTS: The median follow-up time was 6.8 months (range, 5.3-20.2 months). There were 163 occluded aneurysms (84%) and 31 aneurysms with incomplete occlusion (16%). A multivariate analysis showed that type B aneurysm was a risk factor for incomplete occlusion in the PED-only group (odds ratio [OR] 4.854, 95% confidence interval [CI] 1.878-12.548, P = 0.001). Visual symptoms at final follow-up correlated with preoperative visual symptoms (OR 22.777, 95% CI 3.115-166.555, P = 0.002). CONCLUSIONS: Type B aneurysm is associated with a lower occlusion rate after PED-only treatment. Patients with preoperative visual symptoms should be treated promptly to avoid permanent visual symptoms.

Seizure prophylaxis following aneurysmal subarachnoid haemorrhage (SPSAH): study protocol for a multicentre randomised placebo-controlled trial of short-term sodium valproate prophylaxis in patients with acute subarachnoid haemorrhage.

INTRODUCTION: Seizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping. METHODS AND ANALYSIS: In this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0-2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat. ETHICS AND DISSEMINATION: This study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR. TRIAL REGISTRATION NUMBER: ChiCTR.org identifier: ChiCTR2100050161.

Endovascular Management of Vertebrobasilar Trunk Artery Large Aneurysms: Complications and Long-Term Results.

OBJECTIVE: To analyze the complications and long-term results of endovascular management of vertebrobasilar trunk large (≥10 mm) aneurysms (VBTLAs) and identify predictors of outcomes. METHODS: Between 2014 and 2020, 6,987 patients with intracranial aneurysms were referred to our center for aneurysm management and 2,224 patients have undergone the endovascular procedures. We retrospectively reviewed the database and identify all the patients with VBTLAs. RESULTS: A total of 62 VBTLAs were identified. The median aneurysm size was 13.4 mm [interquartile range (IQR) 11.5-18.7]. Among them, 24 aneurysms were treated with overlapping stent techniques, 18 aneurysms were treated with flow diversion, 14 aneurysms were treated with single stent-assisted coiling, and 6 aneurysms were treated with coiling alone. Ten patients were treated with parent artery occlusion or unilateral vertebral artery occlusion. Periprocedural complications were occurred in 7 (11.3%) patients. Clinical follow-up was obtained at the median of 27.5 months (IQR 15.3-58.5). The overall complication rate was 16.1% (10/62), including nine ischemic events and one hemorrhagic event. The combined disability and neurological mortality rate was 12.9% (8/62), with 4 (6.5%) deaths. The favorable outcome rate at follow-up was 87.1% (54/62). The complication-free cumulative survival rates at 1 and 5 years were 86.8 and 82.0%, respectively. The overall cumulative survival rates at 1 and 5 year were 96.5 and 89.8%, respectively. In the multivariate Cox regression analysis, longer procedure time (>115 min) (P = 0.037) and ischemic onset (P = 0.005) predict complications. Angiography follow-up was available for 36 patients at the median of 6.0 months (IQR 6-12), with a complete occlusion rate of 77.8% (28/36). Two (5.6%) aneurysms were recanalized and subsequently received the retreatment. Subgroup analysis did not find any differences in the complete occlusion rate between endovascular strategies. CONCLUSION: Endovascular management of VBTLAs has a reasonable safety profile with favorable 5-year cumulative survival rates and imaging outcomes at follow-up. Prolonged procedure and ischemic onset are associated with a high risk of overall complications.

Time correlation of success recanalization for endovascular recanalization of medically refractory non-acute intracranial arterial occlusions.

Background and purpose: The management of patients with symptomatic non-acute atherosclerotic intracranial artery occlusion (sNAA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy, has been clinically challenging. A number of small-sample clinical studies have discussed endovascular recanalization for sNAA-ICAO and the lack of a uniform standard of operation time. The purpose of this study was to investigate the time correlation of successful recanalization. Methods: From January 2013 to August 2021, 69 consecutive patients who underwent endovascular recanalization for sNAA-ICAO were analyzed retrospectively in the First Affiliated Hospital of Harbin Medical University. The technical success rate, periprocedural complications, and rate of TIA/ischemic stroke during follow-up were evaluated. Results: The overall technical success rate was 73.91% (51/69), and the rate of perioperative complications was 37.68% (26/69). The percentage of patients with perioperative symptoms was 27.53% (19/69). The rate of serious symptomatic perioperative complications was 8.70% (6/69). After adjusting for age, sex, and BMI, the effect of the time from the last symptom to operation on successful recanalization was 0.42 (IQR, 0.20, 0.88, P = 0.021), before the inflection point (51 days). Conclusions: Endovascular recanalization for sNAA-ICAO is technically feasible in reasonably selected patients. The perioperative safety is within the acceptable range. Before 51 days, the last symptoms to operation time, for every 10 days of delay, the probability of successful recanalization is reduced by 57%.