Dimethyl fumarate treatment for unruptured intracranial aneurysms: a study protocol for a double-blind randomised controlled trial.

INTRODUCTION: Intracranial aneurysm (IA) is a common cerebrovascular disease. Considering the risks and benefits of surgery, a significant proportion of patients with unruptured IA (UIA) choose conservative observation. Previous studies suggest that inflammation of aneurysm wall is a high-risk factor of rupture. Dimethyl fumarate (DMF) acts as an anti-inflammatory agent by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and other pathways. Animal experiments found DMF reduces the formation and rupture of IAs. In this study, DMF will be evaluated for its ability to reduce inflammation of the aneurysm wall in high-resolution vessel wall imaging. METHODS AND ANALYSIS: This is a multi-centre, randomised, controlled, double-blind clinical trial. Three hospitals will enrol a total of 60 patients who have UIA with enhanced wall. Participants will be assigned randomly in a 1:1 proportion, taking either 240 mg DMF or placebo orally every day for 6 months. As the main result, aneurysm wall enhancement will be measured by the signal intensity after 6 months of DMF treatment. Secondary endpoints include morphological changes of aneurysms and factors associated with inflammation. This study will provide prospective data on the reduction of UIA wall inflammation by DMF. ETHICS AND DISSEMINATION: This study has been approved by Medical Ethics Committee of the Beijing Tiantan Hospital, Capital Medical University (approval no: KY2022-064-02). We plan to disseminate our research findings through peer-reviewed journal publication and relevant academic conferences. TRIAL REGISTRATION NUMBER: NCT05959759.

Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia.

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

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.

Ticagrelor Versus Clopidogrel in Endovascular Therapy for Cerebral Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Antiplatelet therapy is pivotal in endovascular treatment for intracranial aneurysms. However, there is a lack of studies comparing ticagrelor to clopidogrel in patients with aneurysms undergoing endovascular therapy. Additionally, the existing literature lacks adequate sample size, significant subgrouping, and follow-up, making our study important to cover these gaps. METHODS: We searched 5 databases to collect all relevant studies. Categorical outcomes were pooled as relative risk (R.R.) with a 95% confidence interval (CI). In the single-arm meta-analysis, outcomes were pooled as proportions and their corresponding 95% CI. RESULTS: This comprehensive analysis of 18 studies involving 2,427 patients. For thromboembolic events, the pooled (R.R.) did not show significant differences, whether considering overall events. A similar pattern was observed for thromboembolic events stratified by aneurysmal rupture status, with no significant differences in overall events. Hemorrhagic events did not also exhibit significant differences in previously mentioned stratifications. Furthermore, there were no substantial differences in death and mRS (0-2) on discharge between Ticagrelor and Clopidogrel. Single-arm meta-analyses for Ticagrelor demonstrated low rates of thromboembolic events, hemorrhage, death, and favorable mRS scores, with associated confidence intervals (CIs). Main line of endovascular treatment did not significantly affect either thromboembolic or hemorrhagic outcomes with Ticagrelor and Clopidogrel. CONCLUSIONS: We found no significant differences in key outcomes like thromboembolic events, hemorrhagic events, mortality rates, and favorable mRS (0-2) upon discharge in the studied patients between Ticagrelor and Clopidogrel. Moreover, the single-arm meta-analysis for Ticagrelor revealed low rates of thromboembolic events, hemorrhage, mortality, and high rates of favorable mRS scores.

Perioperative complications of arteriovenous tirofiban administration versus oral dual antiplatelet therapy for stent-assisted embolization treated aneurysmal subarachnoid hemorrhage: A retrospective, controlled cohort analysis.

BACKGROUND: Major perioperative complications of stent-assisted embolization treated for aneurysmal subarachnoid hemorrhage patients include the formation of thromboembolic events (TEs) and hemorrhagic events (HEs), for which antiplatelet protocols play a key role. METHODS: We conducted a single-center retrospective analysis to compare the differences between arteriovenous tirofiban administration with traditional oral dual antiplatelet therapy (DAPT). A total of 417 consecutive patients were enrolled. General clinical characteristics, as well as the perioperative ischemic and hemorrhagic events, were retracted in digital documents. Logistic regression was conducted to identify both risk and protective factors of perioperative TEs and HEs. RESULTS: Perioperative TEs occurred in 21 patients, with an overall perioperative TEs rate of approximately 5.04%; among these patients, the incidence of perioperative TEs in the tirofiban group was less than that in the DAPT group. Additionally, 66 patients developed perioperative HEs, with an incidence of approximately 15.83%; among these patients, the incidence of perioperative HEs was less than that in the DAPT group. No significant differences were seen between the two groups in terms of the mRS score at the time of discharge. CONCLUSION: This study indicated that an improved perioperative antiplatelet drug tirofiban was an independent protective factor for perioperative TEs in stent-assisted embolization of ruptured intracranial aneurysms, but it did not impart an elevated risk of perioperative HEs and had no significant effects on the near-term prognosis of the patients.

Current Mouse Models of Intracranial Aneurysms: Analysis of Pharmacological Agents Used to Induce Aneurysms and Their Impact on Translational Research.

Intracranial aneurysms (IAs) are rare vascular lesions that are more frequently found in women. The pathophysiology behind the formation and growth of IAs is complex. Hence, to date, no single pharmacological option exists to treat them. Animal models, especially mouse models, represent a valuable tool to explore such complex scientific questions. Genetic modification in a mouse model of IAs, including deletion or overexpression of a particular gene, provides an excellent means for examining basic mechanisms behind disease pathophysiology and developing novel pharmacological approaches. All existing animal models need some pharmacological treatments, surgical interventions, or both to develop IAs, which is different from the spontaneous and natural development of aneurysms under the influence of the classical risk factors. The benefit of such animal models is the development of IAs in a limited time. However, clinical translation of the results is often challenging because of the artificial course of IA development and growth. Here, we summarize the continuous improvement in mouse models of IAs. Moreover, we discuss the pros and cons of existing mouse models of IAs and highlight the main translational roadblocks and how to improve them to increase the success of translational IA research.

Glycoprotein IIb/IIIa inhibitors in the treatment of thromboembolic events related to endovascular treatment of cerebral aneurysms-systematic review and meta-analysis.

BACKGROUND AND AIMS: Thromboembolism complication is considered the most common complication associated with the treatment of endovascular. This systematic review and meta-analysis aimed to assess the studies investigating the effect of glycoprotein IIb/IIIa inhibitor agents on thromboembolic complications during endovascular aneurysm coiling. MATERIALS AND METHODS: This systematic review investigated the outcome of the use of three glycoprotein IIb/IIIa inhibitor agents (ie abciximab, tirofiban, and eptifibatide) on the thromboembolic complications during endovascular aneurysm coiling. The electronic databases of PubMed, Web of Science, Scopus, and Medline were searched up to 25 June 2021, using the keywords "Abciximab," "Tirofiban," and "Eptifibatide" incombination with "Thromboembolism Complication," "Aneurysms," and "Endovascular Aneurysm Coiling." RESULTS: A total of 21 articles were found to be eligible and included in this review. The rates of complete and partial recanalization were estimated to be 56% and 92% in patients who underwent abciximab and tirofiban therapy, respectively. Rupture aneurysms were found in the majority of patients. In general, the mortality rate of the patients treated for thromboembolic complications during endovascular treatment of cerebral aneurysms with glycoprotein IIb/IIIa inhibitors was found to be 4.8% (CI 95%:0.027-0.067; p < .005). The average remission rate in studies investigating thromboembolism was 91% (CI 95%:0.88-0.95, I2 : 65.65/p < .001). CONCLUSION: Based on the obtained results, a higher mean rate of complete recanalization by eptifibatide was found in studies in which abciximab or tirofiban were used, compared to other mentioned agents. Moreover, the amount of hemorrhage was reported to be less after using tirofiban rather than abciximab.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. METHODS: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). RESULTS: A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). CONCLUSIONS: In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

Duration of dual-antiplatelet therapy after stent-assisted coil for unruptured intracranial aneurysm: A nationwide cohort study.

BACKGROUND: Stent-assisted coil (SAC) is increasingly used to treat unruptured intracranial aneurysm (UIA). However, the optimal duration of dual-antiplatelet therapy (DAPT) after SAC insertion remains unknown. AIM: To assess the time-dependent effect of DAPT on the risk of ischemic and hemorrhagic complications after SAC. METHODS: This is a retrospective cohort study among patients with UIA treated with SAC using the nationwide health claims database in South Korea between 2009 and 2020. Multivariate Cox regression analysis was used, which included the use of DAPT as a time-dependent variable. The effect of DAPT was investigated for each period of "within 90 days," "91 to 180 days," "181 to 365 days," and "366 to 730 days" after SAC. The primary outcome was a composite of ischemic stroke and major bleeding in each period within two years after SAC. RESULTS: Of the 15,918 patients, mean age at SAC was 57.6 ± 10.8 years, and 3815 (24.0%) were men. The proportion of patients on DAPT was 79.4% at 90 days, 58.3% at 180 days, and 28.9% at 1 year after SAC. During the 2 years after SAC, the primary composite outcome occurred in 356 patients (2.2%). DAPT significantly reduced the primary composite outcome within 90 days after SAC (adjusted hazard ratio (aHR), 0.44; 95% confidence interval (CI), 0.28-0.69; p < 0.001); however, this was not the case after 90 days (all p > 0.05). DAPT reduced ischemic stroke risk within 90 days (aHR, 0.31; 95% CI 0.18-0.54; p < 0.001), and 91 to 180 days after SAC (aHR 0.40; 95% CI 0.18-0.88; p = 0.022); however, after 180 days, DAPT was no longer beneficial. CONCLUSIONS: In patients with UIA treated with SAC, 3 months of DAPT was associated with a decreased risk of the composite of ischemic and hemorrhagic complications.

Efficacy and Safety of Dual Antiplatelet Therapy with the Routine Use of Prasugrel for Flow Diversion of Cerebral Unruptured Aneurysms.

PURPOSE: Prasugrel is not approved for patients treated with flow diverters, which have a high metal coverage ratio. However, robust antiplatelet therapy with prasugrel may prevent thromboembolic complications. We administered prasugrel and aspirin to all patients treated with flow diverters and reported the safety of the antiplatelet therapy regimen. METHODS: This retrospective, single-center study evaluated the angiographic and clinical data of consecutive patients treated with flow diverters for cerebral unruptured aneurysms between June 2020 and May 2022. All patients received dual antiplatelet therapy, including prasugrel and aspirin. The administration of prasugrel ended 3 or 6 months after the procedure, whereas aspirin use continued for at least 12 months. Periprocedural complications (< 30 days post-procedure) and delayed complications (> 30 days post-procedure) were recorded. RESULTS: During the study period, 120 unruptured aneurysms were treated with flow diverters in 110 patients. All patients, except one, survived longer than 12 months after the procedure. The rate of thromboembolic complications was 6.4%, and more than half of the patients had transient symptoms; one (0.9%) had a major ischemic stroke. One patient (0.9%) each had an asymptomatic, small subarachnoid hemorrhage and significant hemorrhagic complications with melena. The rate of permanent neurological deficits was 1.8%, and the mortality rate was 0.9%. CONCLUSIONS: Dual antiplatelet therapy comprising routine use of prasugrel and aspirin for flow diverter-implanted patients possibly contributed to a low rate of thromboembolic complications and low risk of hemorrhagic complications.

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis.

BACKGROUND: The use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. METHODS: Online electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. RESULTS: Five studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants' enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 - 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 - 1.50; P = 0.32) when compared to DAPT with clopidogrel. CONCLUSION: At one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.

Perioperative Low-Dose Aspirin Management for Planned Clipping Surgery: When, How Long, and With What Precautions?

BACKGROUND AND OBJECTIVE: Perioperative low-dose aspirin (ASA) management for open craniotomy surgery lacked information. We analyze to establish the perioperative ASA strategy to minimize both hemorrhagic and thromboembolic complications. METHODS: The investigators designed a multicenter retrospective study, which included patients scheduled to have clipping surgery for unruptured intracranial aneurysm. The incidence and risk factors were analyzed for postoperative hemorrhagic complications and major cardio- and cerebrovascular events (MACCEs) within 1 month postoperation. RESULTS: This study included 503 long-term ASA users of 3654 patients at three tertiary centers. The incidence of hemorrhagic complications and MACCEs was 7.4% (37/503) and 8.8% (44/503), respectively. Older age (>70 years, odds ratio [OR]: 2.928, 95% CI [1.337-6.416]), multiple aneurysms operation (OR: 2.201, 95% CI [1.017-4.765]), large aneurysm (>10 mm, OR: 4.483, 95% CI [1.485-13.533]), and ASA continuation (OR: 2.604, 95% CI [1.222-5.545]) were independent risk factors for postoperative hemorrhagic complications. Intracranial hemorrhage was the only type of hemorrhagic complication that increased in the ASA continuation group (10.6% vs 2.9%, P = .001). Between the ASA continuation and discontinuation groups, the overall incidence of MACCEs was not significantly different (log-rank P = .8). In the subgroup analysis, ASA discontinuation significantly increased the risk of MACCEs in the secondary prevention group (adjusted hazard ratio: 2.580, 95% CI [1.015-6.580]). CONCLUSION: ASA continuation increased the risk of postoperative intracranial hemorrhage. Simultaneously, ASA discontinuation was the major risk factor for postoperative MACCEs in the high-risk group. Without evidence of intracranial hemorrhage, early ASA resumption was indicated (a total cessation duration <7-10 days) in the secondary prevention group.

Perioperative Antiplatelet Management in the Flow-Diverter Treatment for Unruptured Cerebral Aneurysms: A Single-Center, Retrospective Analysis.

BACKGROUND: Although periprocedural antiplatelet therapy for the treatment of unruptured intracranial aneurysms (UIAs) using flow-diverter stents (FDSs) is necessary to avoid thromboembolic complications, a definite antiplatelet therapy has not been established. We aimed to evaluate the safety and efficacy of periprocedural antiplatelet management in UIA treatment with FDS. METHODS: A single-center retrospective analysis of consecutive patients with UIAs treated with FDSs between September 2013 and January 2022 was conducted. Patients received dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) for 14-day before and 3-6 months after FDS placement. Platelet aggregation was evaluated prior to treatment using light transmission aggregometry, which was classified into 3 grades; 1-3: promoted, 4-6: appropriate, and 7-9: non-responder, for adenosine diphosphate (ADP) and collagen. By this classification, the antiplatelet regimen was modified. Outcome included hemorrhagic and ischemic events. RESULTS: 193 patients with 200 UIAs underwent 213 FDSs placement. The median platelet aggregability grade before treatment was 5 for ADP and 4 for collagen. Antiplatelet therapy modification was performed in 62 patients (32.1%). The median postoperative DAPT duration was 94 days. Antiplatelet medicine-related hemorrhagic events occurred in 4 patients (2.1%) and ischemic events occurred in 6 patients (3.1%). These patients had no morbido-mortality. CONCLUSIONS: Periprocedural antiplatelet management based on the value of platelet aggregability was relatively safe and effective for treating UIA with FDS.

Safety of dual antiplatelet therapy in the acute phase of aneurysmal subarachnoid hemorrhage: a propensity score-matched study.

OBJECTIVE: With the evolution of neuroendovascular treatments, there is a great trend to treat acutely ruptured wide-necked aneurysms with stent-assisted coiling (SAC) and flow diverters (FDs), which inevitably requires dual antiplatelet therapy (DAPT). This therapy can increase the rate of hemorrhagic complications following other neurosurgical maneuvers, such as external ventricular drain (EVD) placement or removal. In this study, the authors aimed to evaluate the safety of DAPT in patients with aneurysmal subarachnoid hemorrhage (SAH) treated with SAC or FDs and the therapy's potential benefit in reducing cerebral ischemia and cerebral vasospasm. METHODS: In this retrospective study, the authors reviewed the records of patients who had been admitted to their hospital with acute aneurysmal SAH and treated with SAC, FDs, and/or coiling between 2012 and 2022. Patients were classified into two groups: a DAPT group, including patients who had received DAPT for SAC or FDs, and a non-DAPT group, including patients who had not received any antiplatelet regimen and had been treated with coiling. Perioperative hemorrhagic and ischemic complications and clinical outcomes were compared between the two groups. RESULTS: From among 938 cases of acute ruptured aneurysms treated during 10 years of study, 192 patients were included in this analysis, with 96 patients in each treatment group, after propensity score matching. All basic clinical and imaging characteristics were equivalent between the two groups except for the neck size of aneurysms (p < 0.001). EVD-related hemorrhage was significantly higher in the DAPT group than in the non-DAPT group (p = 0.035). In most patients, however, the EVD-related hemorrhage was insignificant. Parent artery or stent-induced thrombosis was higher in the DAPT group than in the non-DAPT group (p = 0.003). The rate of cerebral ischemia was slightly lower in the DAPT group than in the non-DAPT group (11.5% vs 15.6%, p = 0.399). In the multivariate analysis, cerebral ischemia, rebleeding before securing the aneurysm, extracranial hemorrhage, and cerebral vasospasm were the predictive factors of a poor clinical outcome (p < 0.001, p < 0.001, p = 0.038, and p = 0.038, respectively). CONCLUSIONS: The DAPT regimen may be safe in the setting of acute aneurysmal SAH. Although EVD-related hemorrhage is more common in the DAPT group than the non-DAPT group, it is usually insignificant without any neurological deficit.

To use or not to use antithrombotics in unruptured cerebrovascular malformations? A systematic review focusing on this clinical and surgical dilemma.

OBJECTIVE: Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease. METHODS: The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear. CONCLUSIONS: The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.

Delayed ischemic events with low-dose prasugrel medication for stent-assisted coil embolization in intracranial aneurysm patients.

OBJECTIVE: Much emphasis has been put on the use of antiplatelet medication for the prevention of ischemic events in the treatment of cerebral aneurysms with stent assistance. In this regard, the effectiveness and safety of a low-dose prasugrel regimen during the periprocedural period was recently reported. The purpose of this study was to present the outcomes of patients on low-dose prasugrel regimens during the follow-up period after stent-assisted coil embolization (SACE) of cerebral aneurysms. METHODS: For the 396 consecutive patients undergoing SACE procedures, low-dose prasugrel therapy (5 mg of prasugrel and 100 mg of aspirin) was recommended for 3 months after the endovascular treatment. The authors performed a retrospective review of a single-center experience focusing on delayed ischemic events beyond 1 month after treatment. The mean follow-up period was 24.6 ± 11.3 months. RESULTS: In this cohort of patients on a low-dose prasugrel regimen, cerebral infarction occurred in 1 patient (0.3%, 95% CI 0%-1.8%) beyond 1 month after SACE. No intracranial hemorrhage occurred. Overall ischemic events occurred in 14 patients (3.5%, 95% CI 2.1%-5.9%), all within 6 months of the coiling procedure. All patients had transient symptoms. The events occurred within 2 months after cessation of prasugrel in 11 patients (78.6%). Prasugrel maintenance for 6 months was found to result in lower ischemic events compared with maintenance for 3 months. CONCLUSIONS: For patients undergoing SACE, a low-dose prasugrel regimen was a safe and reliable treatment option for the prevention of delayed ischemic events. Transient ischemic events often occurred within 2 months of stopping prasugrel medication.

Does the clopidogrel CYP2C19 genotype assay predict postprocedure stenosis in cerebral aneurysms treated with a flow diverter?

OBJECTIVE: Flow diverters have emerged as a popular modality for treating cerebral aneurysms but require dual antiplatelet therapy (DAPT) after placement. Clopidogrel is a common choice but is a prodrug that some patients may not convert into an active metabolite. The CYP2C19 genotype assay is used to predict activation speed; however, limited data exist showcasing whether this genotype accurately predicts postprocedure complications after flow diversion treatment of cerebral aneurysms. Therefore, the authors sought to characterize whether CYP2C19 genotype correlated with the development of postprocedure intimal hyperplasia (stenosis) after flow diverter placement. METHODS: Medical records were reviewed for patients who underwent flow diverter treatment of cerebral aneurysm at a single academic institution between January 1, 2012, and May 31, 2020. Patient demographics and comorbidities were reviewed alongside CYP2C19 genotype assay, DAPT regimen, and postprocedure angiogram data. Stenosis was defined based on review of angiogram data by two independent physicians. RESULTS: In this review of 120 unique cerebral aneurysms, 102 received DAPT with clopidogrel and 18 received DAPT with an alternative agent. Stenosis was present on 3-month follow-up angiogram for 35/102 (34.3%) aneurysms receiving DAPT with clopidogrel and in 11/18 (61.1%) aneurysms receiving an alternative DAPT regimen (p = 0.031). The CYP2C19 genotype did not correlate with postprocedure stenosis (p = 0.35). CONCLUSIONS: Clopidogrel was a significantly more effective DAPT agent for preventing stenosis when compared to nonclopidogrel DAPT regimens. The clopidogrel CYP2C19 genotype did not predict postprocedure stenosis in this cohort of 120 cerebral aneurysms treated with a flow diverter.

[A Case Report on Subarachnoid Hemorrhage Secondary to Neurobrucellosis in a Patient with Cerebral Aneurysm]. / Serebral Anevrizmali Hastada Nörobrusellozise Sekonder Subaraknoid Kanama: Olgu Sunumu.

Brucellosis is a multisystemic infection produced by a gram-negative bacillus that can develop a variety of clinical symptoms and complications. Involvement of the central nervous system is a challenging and dangerous consequence of systemic brucellosis. The neurobrucellosis clinical spectrum can be classified as central and peripheral. Meningitis, encephalitis, polyradiculoneuritis, cranial nerve involvement, depression, abscess and cerebrovascular events are some of the potential complications that may develop. The link between neurobrucellosis and cerebrovascular accident has been reported infrequently in the literature. In this report, a case of neurobrucellosis confirmed by cerebrospinal fluid agglutination test and who developed subarachnoid hemorrhage associated with cerebral aneurysm, which is a rare condition in its course was presented. Serum Rose Bengal test and serum Brucella standard tube agglutination (STA) tests were positive at a titer of 1/640 in a 38-year-old male patient who had complaints of fever, sweating, myalgia, arthralgia, weakness, head-neck-back pain and difficulty in walking for 14 days. On magnetic resonance imaging, Brucella sacroiliitis was identified. The patient's fever, head and neck pain continued and nuchal rigidity was found to be positive. Neurobrucellosis was diagnosed based on the cerebrospinal fluid (CSF) examination, which revealed a high white blood cell count, high protein, low glucose level, and STA in CSF at 1/640 titers. Imaging of the brain was conducted concurrently with cerebrospinal fluid analysis indicated subarachnoid hemorrhage caused by cerebral aneurysm rupture. In addition to the medical treatment, the aneurysm rupture was closed with surgical intervention. Three months of simultaneous triple antibiotic treatment were administered to the patient. In the third month of the treatment, the patient was completely cured and no longer had any problems. Although uncommon, subarachnoid hemorrhage due to aneurysm rupture is one of the cerebrovascular consequences of neurobrucellosis. In the process of differential diagnosis of cerebrovascular occurrences, particularly in areas where brucellosis is an endemic disease, it is important to keep in mind that neurobrucellosis can imitate a variety of diseases and cause cerebrovascular events.