Flow diversion of ruptured intracranial aneurysms: a single-center study with a standardized antithrombotic treatment protocol.

BACKGROUND: The use of antithrombotic medication following acute flow diversion for a ruptured intracranial aneurysm (IA) is challenging with no current guidelines. We investigated the incidence of treatment-related complications and patient outcomes after flow diversion for a ruptured IA before and after the implementation of a standardized antithrombotic medication protocol. METHODS: We conducted a single-center retrospective study including consecutive patients treated for acutely ruptured IAs with flow diversion during 2015-2023. We divided the patients into two groups: those treated before the implementation of the protocol (pre-protocol) and those treated after the implementation of the protocol (post-protocol). The primary outcomes were hemorrhagic and ischemic complications. A secondary outcome was clinical outcome using the modified Ranking Scale (mRS). RESULTS: Totally 39 patients with 40 ruptured IAs were treated with flow diversion (69% pre-protocol, 31% post-protocol). The patient mean age was 55 years, 62% were female, 63% of aneurysms were in the posterior circulation, 92% of aneurysms were non-saccular, and 44% were in poor grade on admission. Treatment differences included the use of glycoprotein IIb/IIIa inhibitors (pre-group 48% vs. post-group 100%), and the use of early dual antiplatelets (pre-group 44% vs. 92% post-group). The incidence of ischemic complications was 37% and 42% and the incidence of hemorrhagic complications was 30% and 33% in the pre- and post-groups, respectively, with no between-group differences. There were three (11%) aneurysm re-ruptures in the pre-group and none in the post-group. There were no differences in mortality or mRS 0-2 between the groups at 6 months. CONCLUSION: We found no major differences in the incidence of ischemic or hemorrhagic complications after the implementation of a standardized antithrombotic protocol for acute flow diversion for ruptured IAs. There is an urgent need for more evidence-based guidelines to optimize antithrombotic treatment after flow diversion in the setting of subarachnoid hemorrhage.

Effects of Tranexamic Acid in Patients with Subarachnoid Hemorrhage in Brazil: A Prospective Observational Study with Propensity Score Analysis.

BACKGROUND: Rebleeding from a ruptured aneurysm increases the risk of unfavorable outcomes after subarachnoid hemorrhage (SAH) and is prevented by early aneurysm occlusion. The role of antifibrinolytics before aneurysm obliteration remains controversial. We investigated the effects of tranexamic acid on long-term functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: This was a single-center, prospective, observational study conducted in a high-volume tertiary hospital in a middle-income country from December 2016 to February 2020. We included all consecutive patients with aSAH who either received or did not receive tranexamic acid (TXA) treatment. Multivariate logistic regression analysis using propensity score was used to evaluate the association of TXA use with long-term functional outcomes, measured by the modified Rankin Scale (mRS) at 6 months. RESULTS: A total of 230 patients with aSAH were analyzed. The median (interquartile range) age was 55 (46-63) years, 72% were women, 75% presented with good clinical grade (World Federation of Neurological Surgeons grade 1-3), and 83% had a Fisher scale of 3 or 4. Around 80% of patients were admitted up to 72 h from ictus. The aneurysm occlusion method was surgical clipping in 80% of the patients. A total of 129 patients (56%) received TXA. In multivariable logistic regression using inverse probability treatment weighting, the long-term rate of unfavorable outcomes (modified Rankin scale 4-6) was the same in the TXA and non-TXA groups (61 [48%] in TXA group vs. 33 [33%] in non-TXA group; odds ratio [OR] 1.39, 95% confidence interval [CI] 0.67-2.92; p = 0.377). The TXA group had higher in-hospital mortality (33 vs. 11% in non-TXA group; OR 4.13, 95% CI 1.55-12.53, p = 0.007). There were no differences between the groups concerning intensive care unit length of stay (16 ± 11.22 days in TXA group vs. 14 ± 9.24 days in non-TXA group; p = 0.2) or hospital (23 ± 13.35 days in TXA group vs. 22 ± 13.36 days in non-TXA group; p = 0.9). There was no difference in the rates of rebleeding (7.8% in TXA group vs. 8.9% in non-TXA group; p = 0.31) or delayed cerebral ischemia (27% in TXA group vs. 19% in non-TXA group; p = 0.14). For the propensity-matched analysis, 128 individuals were selected (64 in TXA group and 64 in non-TXA group), and the rates of unfavorable outcomes at 6 months were also similar between groups (45% in TXA group and 36% in non-TXA group; OR 1.22, 95% CI 0.51-2.89; p = 0.655). CONCLUSIONS: Our findings in a cohort with delayed aneurysm treatment reinforce previous data that TXA use before aneurysm occlusion does not improve functional outcomes in aSAH.

Association of calcium channel blockers with lower incidence of intracranial aneurysm rupture and growth in hypertensive patients.

OBJECTIVE: Calcium channel blockers (CCBs) are antihypertensive agents with potential vascular protection effects. This study investigated whether CCB usage was associated with a lower incidence of unruptured intracranial aneurysm (UIA) instability (growth and rupture) in patients with hypertension. METHODS: UIA patients were included in two prospective, multicenter cohort studies (IARP-CP and 100-Project cohorts). All patients received conservative treatment and were regularly followed up every 6 months by CT angiography for 2 years. Patients taking CCBs at least 5 days per week were considered CCB users; otherwise, they were considered non-CCB users. The primary endpoint was UIA instability (rupture, growth of > 20% and/or 1 mm in any dimension, or appearance of a new dome irregularity on imaging follow-up). RESULTS: A total of 392 UIA patients with hypertension (191 male, 201 female; median age 57 years) were included with a mean follow-up duration of 21.7 ± 5.2 months. The primary endpoint was met in 81 patients (20.7%) during follow-up, including 68 patients with aneurysms that grew and 13 with aneurysms that ruptured. CCB users had a lower UIA instability rate than non-CCB users (27/237 [11.4%] vs 54/155 [34.8%], p < 0.001). Multivariable Cox analysis demonstrated that CCB use was associated with a lower risk of UIA instability (HR 0.37, 95% CI 0.22-0.61; p < 0.001). The protective effect of CCB use was consistent in patients taking a single antihypertensive agent (HR 0.22, 95% CI 0.12-0.40; p < 0.001) and patients taking > 1 antihypertensive agent (HR 0.42, 95% CI 0.20-0.87; p = 0.021). For patients with controlled hypertension, CCB use was still associated with a lower risk of UIA instability (HR 0.22, 95% CI 0.09-0.52; p = 0.001). CONCLUSIONS: In UIA patients with hypertension, CCB use was associated with a lower incidence of aneurysm instability.

[Current Knowledge on the Genetic Analysis and Development of Medical Therapy for Intracranial Aneurysms].

Genetic studies on intracranial aneurysms(IAs), like genome-wide association studies, or studies analyzing familial intracranial aneurysms, have successfully revealed the potential contribution of a set of genes to the pathology of IAs. Some of the genes may promote the formation of IAs or the process leading to rupture of the lesions through exacerbating inflammatory responses or facilitating the degenerative changes of arterial walls. Many genes or single-nucleotide polymorphisms have been identified through extensive analyses, but they can only explain one-fifth of the IA pathology; therefore, the pathogenesis of IAs is influenced by many factors, including environmental factors, and not only genetic ones. Intriguingly, a somatic mutation in the PDGFRB gene has recently been identified in more than half of the cases with fusiform aneurysms, making the development of medical therapy targeting PDGFRß signaling realistic. Nowadays, following a series of recent experimental studies, IA is considered a chronic inflammatory disease affecting intracranial arteries, indicating the potential of anti-inflammatory drugs as therapeutic drugs for the treatment of IAs. No wonder, recently published observational studies have revealed the preventive effect of statins and aspirin, with potent anti-inflammatory effects on the rupture of IAs.

Impact of pre-ictal antiplatelet therapy use in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: There is limited evidence on the use of antiplatelet therapy (APT) to reduce the risk and morbidity of cerebral aneurysmal rupture. This analysis retrospectively assessed APT use in patients presenting to our institution with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We evaluated the records of 186 patients over 7 years of retrospective data from our tertiary care center and an existing database of patients with aSAH. A total of 18 cases with patients on APT and 168 patients not on APT (controls) were identified. Primary outcomes measured were clinical grade (Hunt and Hess score), radiographic grade (Fisher score), and presence of delayed cerebral ischemia (DCI). Secondary outcomes were modified Rankin score at discharge and at 3 months. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment or a decrease in at least 2 points on the Glasgow Coma Scale. Logistic regression models were generated. RESULTS: We found that APT use did not appear to lead to statistically significant differences in initial presentation, including Hunt-Hess score and Fisher grade (2.91 vs 3.06, p = 0.66, and 3.23 vs 3.22, p = 0.96 respectively). In addition, APT use was not associated with increased rates of delayed cerebral ischemia (DCI) (OR 0.27 p = 0.12). Our analysis showed that increased Hunt Hess score and the presence of DCI are both associated with increased mRS at 90 days (OR 2.32 p < 0.001; OR 2.91 p = 0.002). CONCLUSION: The patients in this retrospective observational study did not demonstrate worse outcomes from their aSAH despite APT therapy. Larger prospective studies should be performed to see if this relationship holds and if decreased rates of DCI can be observed.

Candidate drugs for preventive treatment of unruptured intracranial aneurysms: A cross-sectional study.

BACKGROUND AND PURPOSE: Establishment of drug therapy to prevent rupture of unruptured intracranial aneurysms (IAs) is needed. Previous human and animal studies have gradually clarified candidate drugs for preventive treatment of IA rupture. However, because most of these candidates belong to classes of drugs frequently co-administered to prevent cardiovascular diseases, epidemiological studies evaluating these drugs simultaneously should be performed. Furthermore, because drugs included in the same class may have different effects in terms of disease prevention, drug-by-drug assessments are important for planning intervention trials. MATERIALS AND METHODS: We performed a cross-sectional study enrolling patients diagnosed with IAs between July 2011 and June 2019 at our institution. Patients were divided into ruptured or unruptured groups. The drugs investigated were selected according to evidence suggested by either human or animal studies. Univariate and multivariate logistic regression analyses were performed to assess the association of drug treatment with rupture status. We also performed drug-by-drug assessments of the association, including dose-response relationships, with rupture status. RESULTS: In total, 310 patients with ruptured and 887 patients with unruptured IAs were included. Multivariate analysis revealed an inverse association of statins (odds ratio (OR), 0.54; 95% confidence interval (CI) 0.38-0.77), calcium channel blockers (OR, 0.41; 95% CI 0.30-0.58), and angiotensin II receptor blockers (ARBs) (OR, 0.67; 95% CI 0.48-0.93) with ruptured IAs. Moreover, inverse dose-response relationships with rupture status were observed for pitavastatin and rosuvastatin among statins, benidipine, cilnidipine, and amlodipine among calcium channel blockers, and valsartan, azilsartan, candesartan, and olmesartan among ARBs. Only non-aspirin non-steroidal anti-inflammatory drugs were positively associated with ruptured IAs (OR, 3.24; 95% CI 1.71-6.13). CONCLUSIONS: The present analysis suggests that several types of statins, calcium channel blockers, and ARBs are candidate drugs for preventive treatment of unruptured IAs.

Pharmacological inhibition of STAT3 by BP-1-102 inhibits intracranial aneurysm formation and rupture in mice through modulating inflammatory response.

As an inhibitor of STAT3, BP-1-102 can regulate the inflammation response caused by vascular smooth muscle cells (VSMCs) by inhibiting the JAK/STAT3/NF-κB pathway, thereby attenuating the symptoms of intracranial aneurysm (IA). IA mouse model was established by stereotactic injection of elastase to evaluate the effect of BP-1-102. The expression levels of smooth muscle markers and matrix metalloproteinases (MMPs) were detected by qRT-PCR, and the levels of inflammatory factors were detected by ELISA and qRT-PCR. The protein levels of the NF-κB signaling pathway factors were examined by Western blot. BP-1-102 reduced blood pressure in aneurysm mice, up-regulated smooth muscle cell markers MHC, SMA, and SM22, and down-regulated the expression of MMP2 and MMP9 in vascular tissues. At the same time, BP-1-102 also down-regulated the expression levels of inflammatory response factors and the NF-κB pathway proteins. In the IA model, BP-1-102 can reduce the expression of inflammatory factors and MMPs bound to NF-κB by inhibiting the activation of the JAK/STAT3/NF-κB pathway proteins, and then restore the vascular wall elastin to reduce blood pressure, thereby treating aneurysm.

The p48 Flow Modulation Device with Hydrophilic Polymer Coating (HPC) for the Treatment of Acutely Ruptured Aneurysms: Early Clinical Experience Using Single Antiplatelet Therapy.

BACKGROUND: Flow diversion (FD) remains a potential treatment option following aneurysmal subarachnoid hemorrhage (aSAH) when standard options may not be feasible. However, it should not be considered a first-line treatment due to the need for dual antiplatelet therapy (DAPT). The hydrophilic polymer coating on the p48MW flow diverter (HPC, phenox) is a surface modification that inhibits platelet adhesion. This study aims to report on our early single-center experience using the p48MW HPC (phenox) flow diverter with single antiplatelet therapy (SAPT) following an aSAH. MATERIALS AND METHODS: We retrospectively identified all patients who had been treated with the p48MW HPC for aSAH under SAPT. All patients treated within 30 days following an aSAH were included. Any occurrence of thromboembolic and hemorrhagic complications was recorded alongside angiographic and clinical follow-up details. RESULTS: Eight patients were identified. The mean interval between aSAH and FD was 6 days. Of the eight ruptured aneurysms, one was blister-like, one saccular, one mycotic, and the remaining five were dissecting aneurysms. Intraprocedural transient thrombus formation was observed in four patients (50%). Stent thrombosis was observed in one patient (12.5%) on day 3 with spontaneous recanalization after being switched onto DAPT. None of the aneurysms rebled after treatment. Two patients died due to cerebral vasospasm. Complete aneurysm occlusion had been achieved in all but one patient at angiographic follow-up (average 6 months). CONCLUSIONS: This small series highlights the possibility and limitations of using the p48MW HPC with SAPT in ruptured aneurysms. Randomized trials with longer follow-up in larger cohorts are underway.

The Safety and Efficacy of Continuous Tirofiban as a Monoantiplatelet Therapy in the Management of Ruptured Aneurysms Treated Using Stent-Assisted Coiling or Flow Diversion and Requiring Ventricular Drainage.

BACKGROUND: Hemorrhagic complications are a major concern for aneurysmal subarachnoid hemorrhage patients treated with stenting or stent-assisted coiling and undergoing additional procedures such as shunting, ventriculostomy placement, and craniotomies/craniectomies. OBJECTIVE: To assess the safety and efficacy of using a continuous infusion of tirofiban as a monoantiplatelet therapy in the management of ruptured aneurysms in the setting of either stent-assisted coiling (SAC) or flow diversion devices (FDD) in patients requiring either an external ventricular drain (EVD) or ventriculoperitoneal shunt (VPS). METHODS: Aneurysmal subarachnoid hemorrhage (aSAH) patients between July 2017 and September 2018 who were treated with SAC or FDD were started on a continuous tirofiban infusion protocol (0.10 µg/kg/min) with no preceding loading dose as a monoantiplatelet therapy. Safety analysis was performed retrospectively to assess the complication rate, hemorrhagic rate, and rate of ischemic events. There were no hemorrhages related to the VPS surgery. RESULTS: Nineteen subjects were included in the series. The patients received a total of 25 procedures that included 19 EVDs and 6 VPSs. Two patients (8.3%) developed small asymptomatic track hemorrhages after EVD placement. One patient developed a large retroperitoneal hemorrhage due to renal artery branch injury during procedure, and another patient developed an idiosyncratic transient thrombocytopenia which resolved after stopping the medication. One patient (4%) developed a transient ischemic attack, which resolved after a bolus of tirofiban. CONCLUSION: Our study suggests that long-term use of intravenous tirofiban monotherapy in aSAH subjects for endovascular SAC or FDD is safe in the perioperative setting.

Efficacy of Statins in Cerebral Vasospasm, Mortality, and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an acute cerebrovascular disease with frequent cerebral vasospasm and delayed cerebral ischemia (DCI). The use of statins for patients with aSAH is controversial. The present study evaluated the efficacy of statins in aSAH-induced vasospasm, DCI, delayed ischemic neurological deficit (DIND), mortality, and other outcomes. METHODS: A literature search was performed in PubMed, EMBASE, and the Cochrane Library. English reports of patients with aSAH who had been treated with statins without combination were included. The outcomes, including cerebral vasospasm, DIND, DCI, mortality, disability, and creatine kinase/alanine aminotransferase/aspartic transaminase elevation, were extracted for meta-analysis. RESULTS: A total of 13 studies, with 776 versus 821 patients treated with statins versus placebo, were retained for the statistical meta-analysis. The results showed that statin administration significantly reduced the frequency of vasospasm (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = 0.003), DIND (RR, 0.76; 95% CI, 0.63-0.91; P = 0.003), vasospasm-DCI (RR, 0.49; 95% CI, 0.32-0.74; P = 0.0008), and mortality (RR, 0.73; 95% CI, 0.54-0.98; P = 0.03). Statins showed insignificant efficacy in the prevention of disability (RR, 0.92; 95% CI, 0.71-1.20), a neurological poor prognosis (RR, 0.75; 95% CI, 0.45-1.27), and creatine kinase/alanine aminotransferase/aspartic transaminase elevation (RR, 1.90; 95% CI, 0.55-6.50). CONCLUSIONS: Statins significantly reduced the incidence of vasospasm, DIND, DCI, and mortality in individuals with aSAH, suggesting its efficacy in aSAH.

Common Data Elements for Unruptured Intracranial Aneurysm and Subarachnoid Hemorrhage Clinical Research: Recommendations from the Working Group on Long-Term Therapies.

OBJECTIVES: The goal for the long-term therapies (LTT) working group (WG) of the Unruptured Intracranial Aneurysm (UIA) and Subarachnoid Hemorrhage (SAH) common data elements (CDEs) was to develop a comprehensive set of CDEs, data definitions, case report forms, and guidelines for use in UIA and SAH LTT clinical research, as part of a new joint effort between the National Institute of Neurological Disorders and Stroke (NINDS) and the National Library of Medicine of the US National Institutes of Health. These UIA and SAH CDEs will join other neurological disease-specific CDEs already developed and available for use by research investigators. METHODS: The eight LTT WG members comprised international UIA, and SAH experts reviewed existing NINDS CDEs and instruments, created new elements when needed, and provided recommendations for future LTT clinical research. The recommendations were compiled, internally reviewed by the all UIA and SAH WGs and steering committee members. The NINDS CDE team also reviewed the final version before posting the SAH Version 1.0 CDE recommendations on the NINDS CDE website. RESULTS: The NINDS UIA and SAH LTT CDEs and supporting documents are publicly available on the NINDS CDE ( https://www.commondataelements.ninds.nih.gov/#page=Default ) and NIH Repository ( https://cde.nlm.nih.gov/home ) websites. The subcommittee members discussed and reviewed various parameters, outcomes, and endpoints in UIA and SAH LTT studies. The following meetings with WG members, the LTT WG's recommendations are incorporated into the disease/injury-related events, assessments and examinations, and treatment/intervention data domains. CONCLUSIONS: Noting gaps in the literature regarding medication and rehabilitation parameters in UIA and SAH clinical studies, the current CDE recommendations aim to arouse interest to explore the impact of medication and rehabilitation treatments and therapies and encourage the convergence of LTT clinical study parameters to develop a harmonized standard.

Intraoperative Mannitol Administration Increases the Risk of Postoperative Chronic Subdural Hemorrhage After Unruptured Aneurysm Surgery.

OBJECTIVE: Although mannitol is used widely to facilitate brain retraction in cases of ruptured aneurysms, there is no consensus about the intraoperative administration of mannitol in the case of unruptured aneurysms. Accordingly, this study was conducted to identify an intraoperative mannitol administration strategy. METHODS: Mannitol was administered routinely to patients (n = 90) from January 2015 to April 2016 and not administered to patients (n = 97) from May 2016 to June 2017. The patient groups with and without mannitol administration were then compared based on the patient medical records, radiologic data, and digital recordings from an intraoperative microscope. RESULTS: The patient groups with and without mannitol administration were comparable regarding patient age, number of elderly patients, sex, and aneurysm locations. No between-group difference was identified in terms of the intradural procedural time, retraction-induced cortical injury, postoperative electrolyte imbalance, symptomatic infarction, and postoperative epidural hematomas. However, the patient group without mannitol administration showed a significantly lower incidence of chronic subdural hematomas (CSDHs) >50 mL (13.3% vs. 3.1%, P = 0.010). Moreover, a multivariate analysis revealed that an advanced age (P = 0.019), male sex (P <0.001), and mannitol administration (P = 0.040) were all statistically significant risk factors for a postoperative CSDH >50 mL following unruptured aneurysm surgery. CONCLUSIONS: Withholding the administration of mannitol during a pterional or modified procedure for unruptured aneurysms was found to reduce the postoperative occurrence of a CSDH without increasing the operative difficulties or other postoperative complications.

Comparison of two preventive dual antiplatelet regimens for unruptured intracranial aneurysm embolization with flow diverter/disrupter: A matched-cohort study comparing clopidogrel with ticagrelor.

PURPOSE: Standard dual antiplatelet therapy (DAPT) for complex aneurysms treated with flow diversion and flow disruption is acetylsalicylic acid (ASA) plus clopidogrel. However, clopidogrel resistance frequently occurs and can lead to thromboembolic events. Ticagrelor is an alternative not requiring platelet inhibition testing. We compared two DAPT regimens (ASA with clopidogrel or ticagrelor) on morbi-mortality, safety and efficacy of unruptured aneurysm embolization with flow diverter/disrupter. MATERIALS AND METHODS: This retrospective analysis of a 1:1 matched cohort compares patients treated with ASA + clopidogrel (March 2013-December 2015) vs. ASA + ticagrelor (January 2016-March 2017). No platelet inhibition testing was conducted. Patients matched for age (±10 years), type of treatment and aneurysm sac size ( ± 2 mm). Primary outcome measures were morbidity and mortality at 1-month; secondary outcomes were thromboembolic and hemorrhagic complications [on angiography and magnetic resonance imaging (MRI)] and groin complications. Outcomes were compared using bivariate analyses. RESULTS: Ninety patients fulfilled inclusion criteria, of which 80 remained after matching (40 per group). There was no statistical difference in 1-month morbidity between the ticagrelor and clopidogrel groups (2.5% vs. 10%, P = 0.36) and no deaths reported. We observed no significant differences between ticagrelor and clopidogrel groups in terms of angiographic thromboembolic complications (5% vs. 12.5%, P = 0.43), territorial infarction on DWI (2.5% vs. 7.5%, P = 0.61), angiographic (0% vs. 0%, P = 1) and MRI (5% vs 5%, P = 1) hemorrhagic complications, new microbleeds (57.5% vs. 40%, P = 0.12) and groin puncture complications (2.5% vs. 0%, P = 1). At three months, there was no delayed territorial infarction or hemorrhage in either group. CONCLUSIONS: Ticagrelor is safe and effective in replacing clopidogrel as DAPT for unruptured aneurysms.

Roles of Nicotine in the Development of Intracranial Aneurysm Rupture.

Background and Purpose- Tobacco cigarette smoking is considered to be a strong risk factor for intracranial aneurysmal rupture. Nicotine is a major biologically active constituent of tobacco products. Nicotine's interactions with vascular cell nicotinic acetylcholine receptors containing α7 subunits (α7*-nAChR) are thought to promote local inflammation and sustained angiogenesis. In this study, using a mouse intracranial aneurysm model, we assessed potential contributions of nicotine exposure and activation of α7*-nAChR to the development of aneurysmal rupture. Methods- Intracranial aneurysms were induced by a combination of deoxycorticosterone-salt induced hypertension and a single-dose elastase injection into cerebrospinal fluid in mice. Results- Exposure to nicotine or an α7*-nAChR-selective agonist significantly increased aneurysm rupture rate. Coexposure to an α7*-nAChR antagonist abolished nicotine's deleterious effect. In addition, nicotine's promotion of aneurysm rupture was absent in smooth muscle cell-specific α7*-nAChR subunit knockout mice but not in mice lacking α7*-nAChR on endothelial cells or macrophages. Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines. α7*-nAChR antagonist reversed nicotine-induced upregulation of these growth factors and cytokines. Conclusions- Our findings indicate that nicotine exposure promotes aneurysmal rupture through actions on vascular smooth muscle cell α7*-nAChR.

Effect of HUK on the outcome of ruptured intracranial aneurysm.

OBJECTIVE: To evaluate the clinical efficacy of Human Urinary Kallidinogenase (HUK) on the outcome of patients with ruptured intracranial aneurysm. METHODS: This was a prospective, open-label study. At the Department of Neurosurgery in our hospital, 127 patients were treated and operated due to ruptured intracranial aneurysm in the period 2015-2016. After surgery, all the patients received basic treatment and 70 patients received additional HUK treatment (HUK group) according to their willing. In detail, 0.15 PNA unit of HUK injection plus 100 ml saline in intravenous infusion was performed, with once a day for 14 consecutive days. The modified Rankin Scale (mRS) scores and favorable mRS rates (mRS 0-1) were analyzed 3-month after the treatment. RESULTS: No difference was shown in the basic characteristics between the two groups (p > 0.05). Favorable mRS rate in the HUK group (71.43%) was significantly higher than that in control group (50.88%, p < 0.05). In addition, 3-month death rate was significantly lower in the HUK group. Delayed ischemic stroke rate was similar between the two groups. CONCLUSION: HUK can reduce morbidity and mortality of patients with ruptured intracranial aneurysm after surgery.

Extracranial-Intracranial High-Flow Bypass for Giant Ruptured Paraclinoid Aneurysm with Concomitant Bilateral Internal Carotid Artery Stenotic Dissection.

BACKGROUND: Giant ruptured paraclinoid aneurysm with concomitant bilateral internal carotid artery dissection (CAD) can be a difficult condition to treat with current surgical and endovascular techniques. Paraclinoid internal carotid artery (ICA) aneurysms remain a major challenge for vascular neurosurgeons. There are still controversies in the management of carotid artery (CA) dissections. Surgical and endovascular treatment is recommended in cases with multivessel dissections or those complicated by subarachnoid hemorrhage (SAH). CASE DESCRIPTION: We report a case of a 35-year-old woman presenting clinical manifestations and tomographic findings compatible with SAH caused by rupture of a paraclinoid aneurysm in the left ICA. We had to treat the ruptured aneurysm and the concurrent dissection of both ICAs. The patient underwent high-flow extracranial-intracranial arterial graft bypass and subsequent trapping of the left ICA. Complete aneurysm exclusion from the cerebral circulation was achieved, and the possible embolic events from the left side were prevented. The concomitant right internal CAD was treated conservatively with anticoagulants and antiplatelets. CONCLUSIONS: Dealing only with the ruptured paraclinoid aneurysm, without taking care of the underlying cerebral ischemia owing to concomitant extracranial ICA dissection, could be an insufficient approach for treatment. In the presented case of a giant ruptured paraclinoid aneurysm and coexistence of severe bilateral ICA dissecting stenosis, trapping with matching the bypass flow was the proper solution for managing simultaneously with the aneurysm and the cerebral ischemia from the left side. Anticoagulants and antiplatelets were applied safely to treat the right internal CAD.

Safety of Prasugrel loading in ruptured blister like aneurysm treated with a Pipeline device.

OBJECTIVE: Blister like aneurysm (BLA) is extremely challenging to treat; endoluminal reconstruction has emerged as the most promising treatment method. When to treat after the ictus, the timing of administration of antiplatelet and causal relationship between platelet function testing results and thrombo-embolism is unclear. We theorized that Prasugrel with a lower incidence of resistance may be a safe suitable alternative to clopidogrel in patients treated with a flow diverter (FD). METHODS: Prospectively collected data from consecutive patients treated for a ruptured blister with an FD was reviewed. Device deployment was timed to be at 2 h following Prasugrel loading. Thrombo-embolic and hemorrhagic complications, and occlusion rates were documented. RESULTS: Nine patients were included. Most were females (55%); the median age was 55 (43, 65). The median Fischer grade was 3 (2, 4). A single pipeline device was deployed in all within 24 h of admission; the median time from ictus to device deployment was 4 days (2, 30). There were no thrombo-embolic or hemorrhagic complication. Complete occlusion was noted in 89% (n = 9). CONCLUSION: Prasugrel loading timed 2 h prior to stent delivery did not increase thrombo-embolic or hemorrhagic complications. Single stent that is well apposed against the wall appears to be an effective treatment strategy to treat BLA. Advances in knowledge: Treatment of acutely ruptured BLA with a single pipeline device deployed at 2 h after Prasugrel loading appears to be safe.

Treatment of Infected Aneurysm with Combined Endovascular Aneurysm Repair and Abscess Drainage.

PURPOSE: To evaluate the clinical utility of combination therapy with endovascular aneurysm repair (EVAR) and abscess drainage for the treatment of infected aneurysms. MATERIALS AND METHODS: Between July 2009 and May 2015, 8 patients underwent combination therapy with EVAR and abscess drainage. There were 5 men and 3 women, with a mean age of 75 years ± 7. Aneurysms were of the thoracic aorta in 5 patients, the abdominal aorta in 2, and the internal iliac artery in 1. Four patients had concurrent infection, including pyelonephritis in 2, pelvic abscess in 1, and suppurative knee arthritis in 1. Three patients had ruptured aneurysms. Abscess drainage was performed percutaneously under computed tomographic guidance in 5 patients, thoracoscopic guidance in 2, and both in 1. RESULTS: Six patients (75%) were discharged without additional intervention except for antibiotic therapy, and the other 2 patients (25%) underwent open repair to control infection and to repair endoleak, respectively. There were no in-hospital deaths. During the mean follow-up period of 48 months ± 22, all patients were alive except for 1 patient who died of recurrence of rectal cancer at 51 months. There were no aorta- or artery-related adverse events. Overall survival rates at 1 and 5 years were 100% and 80%, respectively. Aneurysm-related event-free rates at 1 and 5 years were 75%. CONCLUSIONS: Combination therapy with EVAR and abscess drainage for the treatment of infected aneurysms seems to be a promising strategy as an alternative or "bridge" to open surgery.