Phase 1/2a Trial of ISPASM.

BACKGROUND AND PURPOSE: Microthrombosis could play a role in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Tirofiban has shown promising results in reducing delayed cerebral ischemia in retrospective studies. However, the safety of using tirofiban in aneurysmal subarachnoid hemorrhage is not rigorously established. METHODS: A phase 1/2a double-blinded randomized controlled trial (2:1 randomization) to assess the safety of a 7-day intravenous infusion of tirofiban compared with placebo, in patients with aneurysmal subarachnoid hemorrhage treated with ventriculostomy placed in the operative room and coiling was conducted. The primary end point was any intracranial hemorrhage during the hospital stay. The secondary end points were: incidence of radiographic and clinical vasospasm, incidence of delayed cerebral ischemia, and incidence of cerebral ischemic changes noted on magnetic resonance imaging or computed tomography. RESULTS: Eighteen patients received intravenous tirofiban and 12 received placebo. There was no difference in baseline characteristics except for higher male proportions in the tirofiban group. There was no difference in death, in development of new or change in existing intracranial hemorrhages, in thrombocytopenia, and need for shunts in the two arms. However, the tirofiban arm had a lower incidence of delayed cerebral ischemia compared with placebo (6% [1/18] versus 33% [4/12]; P=0.04), and less radiographic vasospasm as detected by catheter angiogram or computed tomography angiography (P=0.01) and computed tomography perfusion (P=0.01). CONCLUSIONS: The above preliminary results support proceeding with further testing of the safety and efficacy of 7-day intravenous infusion of tirofiban in a pragmatic (placing external ventricular drain by the bedside), multicenter setting, and using a larger population. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03691727.

Concentration of Lp(a) (Lipoprotein[a]) in Aneurysm Sac Is Associated With Wall Enhancement of Unruptured Intracranial Aneurysm.

BACKGROUND AND PURPOSE: Atherosclerotic remodeling of the aneurysm wall, which could be detected as aneurysm wall enhancement (AWE) by magnetic resonance-vessel wall imaging, is a part of degenerative change of unruptured intracranial aneurysms (UIAs). The purpose of this study was to determine whether the luminal concentrations of atherosclerotic proteins in the aneurysm sac were associated with increased wall enhancement of UIAs in vessel wall imaging. METHODS: We performed a prospective study of subjects undergoing endovascular treatments for UIAs. All subjects underwent evaluation using 3T-magnetic resonance imaging, including pre/postcontrast vessel wall imaging of the UIAs. Blood samples were collected from the aneurysm sac and the parent artery during endovascular procedures. Presence/absence of AWE was correlated with the delta difference in concentration for each atherosclerotic protein between the lumen of UIA and in the parent artery. RESULTS: A total of consecutive 17 patients with 19 UIAs were enrolled. The delta difference of lipoprotein(a) was significantly higher in UIAs with AWE compared with those without AWE (-6.9±16.0 versus -45.4±44.9 µg/mL, P=0.03). CONCLUSIONS: Higher luminal concentrations of lipoprotein(a) in the aneurysm sac were significantly associated with increased wall enhancement of UIAs. A larger study is needed to confirm these findings.

Assessment of fluctuating decision-making capacity in individuals with communication barriers: a case study.

A current need exists for research to assist clinicians in the capacity evaluation process, especially in relation to assessment of clients with complex issues such as fluctuating capacity and communication barriers. The aim of this article is to promote knowledge and consideration of these issues through an examination of neuropsychological, ethical, and medical-legal factors associated with the assessment of capacity in an individual with both fluctuating capacity and communication impairments. The discussion includes a narrative case study of a complex individual case seen by the Regional Capacity Assessment Team (RCAT) for an assessment of decision-making capacity related to personal and financial matters. Relevant background information about this client, behavioral observations, neuropsychological test results, and the process and outcome of the RCAT targeted capacity interview are presented. Based on previous literature and the case study, a series of recommendations are provided to guide the clinician through the capacity evaluation process with individuals with complex issues. Common pitfalls, nuances, and dilemmas involved in capacity assessment are addressed.

The butterfly effect: How an outpatient quality improvement project affected inpatient opioid's prescribing habits.

Background: The aim of the study was to assess whether a quality improvement project focused on providers' education of responsible opioid prescribing, creating order sets to facilitate pre- and post-operative adjunct use, and decreasing the number of opioids prescribed following elective outpatient surgery affected opioid prescribing habits and the use of adjunct pain medication on the inpatient Emergency General Surgery (EGS) service. Methods: Inpatient EGS opioid prescribing habits following laparoscopic cholecystectomy, laparoscopic and open inguinal hernia repair, or open umbilical hernia repair during the pre- and post-Acute Care Surgery Division-Quality Improvement (QI) periods were recorded retrospectively. Demographics, type and dose of opioids, and non-opioid adjuncts prescribed were collected. Opioids were converted to oral morphine equivalents (OME). Pre- and post-QI data were compared. Post-QI discharge opioids prescribed were compared to reported use of opioids. Patients' rating of pain management is reported. Results: One hundred twenty-two and 62 patients were included during the pre- and post- QI periods, respectively. Post-QI, opioid prescribing decreased, and adjunct prescribing increased (31.1% vs. 72.6%; p < 0.001) at discharge. Interestingly, higher 24 h pre-discharge OME was associated with a higher OME prescribed at discharge (B = 1.255 [0.377 - 2.134]; p = 0.005). Of the 47 EGS patients who followed up in clinic post-ACS QI, 89.4% rated their pain management as excellent/good, 8.5% as fair, and 2.1% as poor. Conclusions: Implementation of a multifaceted approach to decrease opioid prescribing in the outpatient setting organically affected opioid prescribing habits at discharge for inpatients.

Decreasing opioid prescribing at discharge while maintaining adequate pain management is sustainable.

Background: In 2018, using a pragmatic multimodal approach, discharge opioid prescriptions were reduced without affecting pain control management. Herein, we assessed whether this approach was sustainable and whether discharge opioid prescriptions could be further reduced. Methods: This is a single center prospective study of patients who underwent elective outpatient procedures provided by our institution's Acute Care Surgery Division surgeons. Adult patients who underwent elective surgeries performed by surgeons in the Division of Acute Care Surgery from November 2018 to June 2021 and agreed to participate were included. The opioid prescriptions pre-populated in the order set at discharge were reduced from 20 pills to 10 pills in May 2020. Demographics, opioid information, non-opioid adjuncts prescribed, reported use of opioids prescribed, and patients' satisfaction were collected. Opioids were converted to oral morphine equivalents (OME). Results: A total of 178 patients were included. Elective surgeries performed mainly included inguinal hernia repair (38.8%), laparoscopic cholecystectomy (30.3%), cyst excision (13.5%), and umbilical hernia (8.4%). One hundred twenty-five and 53 patients underwent an elective operation with a surgeon in the Acute Care Surgery Division before and after the number of opioids pre-populated in the order set at discharge was reduced from 20 pills to 10 pills, respectively. Reducing the pre-populated discharge opioid prescriptions led to a significant decrease in OME prescribed (75 [75-76.5] vs. 80 [75-150], p < 0.001) without affecting patients' satisfaction with pain management (excellent/good: 87.8% vs. 84%; p = 0.305). Conclusions: Our pragmatic multimodal approach is sustainable and allows for additional opioid prescription reduction without affecting patients' satisfaction with pain management.

Postoperative cognitive dysfunction after endovascular treatments for unruptured intracranial aneurysms: A pilot study.

OBJECTIVE: Post operative cognitive dysfunction (POCD) has been widely observed after major surgery, particularly in elderly patients with general anesthesia (GA). However, a specific unanswered question is whether different approaches to anesthetic managements are associated with different cognitive outcomes after endovascular treatments for unruptured intracranial aneurysms (UIAs). The purpose of this study is to assess the correlation of POCD with GA versus monitored anesthesia care (MAC). METHODS: We performed a pragmatic, prospective study to assess the association between different anesthetic approaches and POCD. We compared the pre- and post-procedural Montreal Cognitive Assessment (MoCA) scores in patients with normal cognition who underwent treatments of UIAs with various endovascular methods, using either GA or MAC. RESULTS: A total of 23 patients with UIAs were enrolled in the study. Seven (30.4%) and sixteen (69.6%) UIAs were treated without perioperative complications under GA or MAC, respectively. There was a significant decline in the post-procedural MoCA score under GA (mean difference = 1.14; 95% confidence interval = [0.42-1.87], P < 0.01). By contrast, there was no significant difference of MoCA score between pre- and post-procedure under MAC (mean difference = 0.19; 95% confidence interval = [-0.29-0.67], P = 0.59). CONCLUSIONS: Treating UIAs using MAC was associated with a decrease in POCD as compared to GA in patients undergoing endovascular treatments for UIAs with normal cognition. Larger randomized studies are needed to confirm these findings.

Melatonin and risk of mortality in subjects with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a cause of morbidity associated with aneurysmal subarachnoid hemorrhage (aSAH). Neuroinflammation contributes to the development of DCI. Melatonin is a sleep-promoting hormone known to have cerebral anti-inflammatory properties. We hypothesized that synthetic melatonin (or the selective melatonin receptor agonist ramelteon) incidentally prescribed to improve sleep may lower the incidence of DCI among hospitalized aSAH patients. METHODS: Subjects with a Hunt and Hess Grade I-III were identified from a data registry involving all aSAH patients admitted to our hospital between January 2015 and September 1, 2018. A cohort of patients who received either melatonin or ramelteon during their hospitalization was compared to a matched cohort that did not receive these drugs. The primary endpoint was incidence of DCI. Secondary outcomes included modified Rankin score (mRS) at discharge, discharge destination, and mortality at 6 weeks from discharge. The two groups were compared using univariate analysis. P < 0.05 was considered significant. RESULTS: There was no significant difference in the incidence of DCI (15.8% vs. 16.9%, p = 1), discharge mRS (mRS 0-3: 51.3% vs. 45.1%, p = 0.59), discharge disposition (Home: 43.6% vs. 44.4, p = 0.47), or mortality (0% vs. 9.2%; p = 0.074) between the melatonin/ramelteon and non-melatonin groups. CONCLUSION: The use melatonin had no effect on DCI but may improve mortality in aSAH subjects. Prospective studies using a larger cohort are warranted to validate these findings.

Effects of patient-level noise abatement orders on sound levels experienced by critically ill subarachnoid hemorrhage patients: an observational study.

BACKGROUND/OBJECTIVE: Patients with aneurysmal subarachnoid hemorrhage (aSAH) may be at risk for complications related to excessive environmental noise. Our ICU utilizes a variety of universal interventions to minimize ambient noise levels, but patients with aSAH additionally have specific orders intended to further minimize physiologic stress and noise exposure. It is unknown whether such orders can have a supplementary reductive effect on noise exposure. METHODS: Sound levels were measured for at least three consecutive days in the rooms of 17 patients with aSAH and implemented 'subarachnoid precautions' orders. Sound levels were similarly recorded in the rooms of 11 geographically-proximate, critically-ill control patients without aSAH. RESULTS: Linear mixed models were used to assess the difference in measurements between groups. Observations were combined into fifteen-minute windows, then group means and their differences were calculated and plotted to help identify what times of the day had significant differences. aSAH patients consistently experienced lower sound levels than control patients, with a statistically significant difference (p < 0.05) in mean sound levels at 62 of 96 intervals throughout the day. Overall, the mean sound level for aSAH patients was always between 62-63dBA, while the mean sound level experienced by control patients ranged between 64-66dBA. CONCLUSIONS: Implementation of patient-specific orders can have a supplementary reductive effect on noise exposure for aSAH patients in an intensive care unit that already utilizes universal noise abatement interventions.

Tackling the opioid epidemic: Reducing opioid prescribing while maintaining patient satisfaction with pain management after outpatient surgery.

INTRODUCTION: Results of a quality improvement (QI) project to standardize our opioid prescribing practices following five common outpatient general surgery procedures are presented. METHODS: Opioid prescribing habits were reviewed from June to December 2017. QI measures were implemented. We prospectively collected data on opioid prescribing habits and patients' pain management ratings from September 2018 to February 2019. RESULTS: Following implementation, combination pills were less prescribed. More patients were prescribed adjuncts pre- (66% vs. 3%; p < 0.01) and post-operatively (85% vs. 50%; p < 0.01). One-third of pills were prescribed (1363 vs. 4185), with only 520 consumed. Average OME prescribed decreased from 179 to 127 mg (p < 0.001). At follow-up, 52 patients (54%) reported taking 11 pills (1-20) post-operatively for five days. Pain management was rated as good/excellent (88.6%) or fair (9.3%). CONCLUSIONS: Using a pragmatic multimodal approach, decreasing opioid prescriptions at discharge allows for adequate pain management.

Safety and feasibility of the Woven EndoBridge device deployment with monitored anesthesia care.

OBJECTIVE: The Woven EndoBridge (WEB) device can be used for complex intracranial aneurysms (IAs), mostly under general anesthesia (GA). However, it remains controversial if anesthetic management could affect procedural outcomes after endovascular treatments using the WEB for IAs. The purpose of this study is to investigate the safety and feasibility of the WEB deployment for patients under monitored anesthesia care (MAC). METHODS: We reviewed 27 IAs in 25 patients who were treated by using the WEB device from February to December in 2019. Our first-line anesthetic management of patients during the procedures was the MAC. GA was performed based on patient's clinical status or preference. Subjects' demographic data, aneurysms' characteristics, procedure-related complications, grade of stasis after the WEB deployment, duration of procedure, and length of hospital stay were compared between subjects who underwent GA versus those who underwent MAC. RESULTS: Successful deployment of the WEB device was obtained in all patients. In total, 10 and 17 IAs were treated with GA and MAC, respectively. There was no significant difference in demographics (age: p = 0.12, sex: p = 0.54), aneurysms' characteristics (ruptured: p = 1.00, neck width: p = 0.96, aspect ratio: p = 0.98, maximum diameter: p = 0.69), complications (p = 1.00), postprocedural grade of stasis (p = 1.00), duration of the procedure (p = 0.23), and the length of hospital stay (p = 0.81) between GA and MAC. CONCLUSIONS: MAC can be used for the WEB device deployment safely and effectively.

Tirofiban Protocol Protects Against Delayed Cerebral Ischemia: A Case-Series Study.

BACKGROUND: There has not been any effective prophylaxis for delayed cerebral ischemia delayed cerebral ischemia (DCI) since the introduction of nimodipine. Platelet inhibition may reduce the risk by preventing the formation of microthrombi. Tirofiban has been used as a single monotherapy bridge given its safety profile and controlled platelet inhibition. OBJECTIVE: To assess the risk of DCI in aneurysmal subarachnoid hemorrhages (aSAH) patients treated with the tirofiban protocol. METHODS: aSAH patients between December 2010 and March 2019 who were treated with stent assisted coiling or flow-diverting device were started on a continuous tirofiban infusion protocol and were compared with patients who underwent coil embolization without antiplatelet therapy. Safety analysis was performed to assess DCI, hemorrhagic, and ischemic events. RESULTS: A total of 21 patients were included in the tirofiban series and 81 in the control group. There was no statistical difference in age, gender, Hunt-Hess grade, and Fisher scale between the 2 groups except for a higher Fisher grade II in the tirofiban group. Multivariate analysis revealed tirofiban to reduce the risk of vasospasm by 72 percent (OR .28, P = .03), without affecting the risk of hemorrhagic complications (OR = 0.50, P = .26). Tirofiban reduced the risk of symptomatic stroke endovascular procedure but it did not reach significance (P = .06). DCI, older age, and postprocedural symptomatic stroke were significant predictors of mortality. Tirofiban reduced the mortality risk, but this association was not statistically significant. CONCLUSION: The tirofiban protocol in aSAH patients reduces the risk of DCI without conferring additional risks. This supports previous findings were antiplatelet therapy reduced DCI in human and animal models.

Quantitative Susceptibility Mapping and Vessel Wall Imaging as Screening Tools to Detect Microbleed in Sentinel Headache.

BACKGROUND: MR-quantitative susceptibility mapping (QSM) can identify microbleeds (MBs) in intracranial aneurysm (IA) wall associated with sentinel headache (SH) preceding subarachnoid hemorrhage. However, its use is limited, due to associated skull base bonny and air artifact. MR-vessel wall imaging (VWI) is not limited by such artifact and therefore could be an alternative to QSM. The purpose of this study was to investigate the correlation between QSM and VWI in detecting MBs and to help develop a diagnostic strategy for SH. METHODS: We performed a prospective study of subjects with one or more unruptured IAs in our hospital. All subjects underwent evaluation using 3T-MRI for MR angiography (MRA), QSM, and pre- and post-contrast VWI of the IAs. Presence/absence of MBs detected by QSM was correlated with aneurysm wall enhancement (AWE) on VWI. RESULTS: A total of 40 subjects harboring 51 unruptured IAs were enrolled in the study. MBs evident on the QSM sequence was detected in 12 (23.5%) IAs of 11 subjects. All these subjects had a history of severe headache suggestive of SH. AWE was detected in 22 (43.1%) IAs. Using positive QSM as a surrogate for MBs, the sensitivity, specificity, positive predictive value, and negative predictive value of AWE on VWI for detecting MBs were 91.7%, 71.8%, 50%, and 96.6%, respectively. CONCLUSIONS: Positive QSM findings strongly suggested the presence of MBs with SH, whereas, the lack of AWE on VWI can rule it out with a probability of 96.6%. If proven in a larger cohort, combining QSM and VWI could be an adjunctive tool to help diagnose SH, especially in cases with negative or non-diagnostic CT and lumbar puncture.

Aspirin associated with decreased rate of intracranial aneurysm growth.

OBJECTIVE: Aspirin has emerged as a potential agent in the prevention of rupture of intracranial aneurysms (IAs). In this study, the authors' goal was to test if aspirin is protective against aneurysm growth in patients harboring multiple IAs ≤ 5 mm. METHODS: The authors performed a retrospective review of a prospectively maintained database covering the period July 2009 through January 2019. Patients' data were included if the following criteria were met: 1) the patient harbored multiple IAs; 2) designated primary aneurysms were treated by surgical/endovascular means; 3) the remaining aneurysms were observed for growth; and 4) a follow-up period of at least 5 years after the initial treatment was available. Demographics, earlier medical history, the rupture status of designated primary aneurysms, aneurysms' angiographic features, and treatment modalities were gathered. RESULTS: The authors identified 146 patients harboring a total of 375 IAs. At the initial encounter, 146 aneurysms were treated and the remaining 229 aneurysms (2-5 mm) were observed. During the follow-up period, 24 (10.48%) of 229 aneurysms grew. All aneurysms observed to grow later underwent treatment. None of the observed aneurysms ruptured. Multivariate analysis showed that aspirin was significantly associated with a decreased rate of growth (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.05-0.63). Variables associated with an increased rate of growth included hypertension (OR 14.38, 95% CI 3.83-53.94), drug abuse (OR 11.26, 95% CI 1.21-104.65), history of polycystic kidney disease (OR 9.48, 95% CI 1.51-59.35), and subarachnoid hemorrhage at presentation (OR 5.91, 95% CI 1.83-19.09). CONCLUSIONS: In patients with multiple IAs, aspirin significantly decreased the rate of aneurysm growth over time. Additional prospective interventional studies are needed to validate these findings.

Hybrid Surgery for Internal Carotid Artery Revascularization.

OBJECTIVE: The management of chronic complete internal carotid artery (ICA) occlusion (COICA) has been challenging. Endovascular procedures have been performed with variable success and risks, depending on the type of occlusion and distal revascularization. We present a novel hybrid procedure to recanalize the ICA when previous endovascular interventions have failed or been deemed too risky. METHODS: Two patients presented with symptomatic COICA after maximal medical management. They were deemed at high risk of endovascular intervention and/or previous endovascular attempts had failed. Thus, they had indications for a hybrid procedure. RESULTS: A hybrid technique was used to create a stump by surgical endarterectomy, followed by recanalization using an endovascular approach via femoral access. We have described the technique in detail. Postoperative computed tomography perfusion scanning showed normalization of the mean transient time, cerebral blood volume, and cerebral blood flow compared with the preoperative findings. Cerebral angiography showed successful recanalization of the ICA. Neither patient experienced any complications. CONCLUSION: A hybrid technique is feasible and should be considered for patients with COICA in whom maximal medical management has failed and who have a high-risk profile for endovascular intervention or in whom previous endovascular attempts have failed.

External Ventricular Drain and Hemorrhage in Aneurysmal Subarachnoid Hemorrhage Patients on Dual Antiplatelet Therapy: A Retrospective Cohort Study.

BACKGROUND: Stenting and flow diversion for aneurysmal sub arachnoid hemorrhage (aSAH) require the use of dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate whether DAPT is associated with hemorrhagic complication following placement of external ventricular drains (EVD) in patients with aSAH. METHODS: Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received DAPT for stenting or flow diversion, and patients who underwent microsurgical clipping or coiling and did not receive DAPT by way of a backward stepwise multivariate analysis. RESULTS: Four hundred forty-three patients were admitted for aSAH management. Two hundred ninety-eight patients required placement of an EVD. One hundred twenty patients (40%) were treated with stent-assisted coiling or flow diversion and required DAPT, while 178 patients (60%) were treated with coiling without stents or microsurgical clipping and did not receive DAPT. Forty-two (14%) cases of new hemorrhage along the EVD catheter were identified radiographically. Thirty-two of these hemorrhages occurred in patients on DAPT, while 10 occurred in patients without DAPT. After multivariate analysis, DAPT was significantly associated with radiographic hemorrhage [odds ratio: 4.92, 95% confidence interval: 2.45-9.91, P = .0001]. We did not observe an increased proportion of symptomatic hemorrhage in patients receiving DAPT (10 of 32 [31%]) vs those without (5 of 10 [50%]; P = .4508). CONCLUSION: Patients with aSAH who receive stent-assisted coiling or flow diversion are at higher risk for radiographic hemorrhage associated with EVD placement. The timing between EVD placement and DAPT initiation does not appear to be of clinical significance. Stenting and flow diversion remain viable options for aSAH patients.

In vitro accuracy and inter-observer reliability of CT angiography in detecting intracranial aneurysm enlargement.

BACKGROUND AND PURPOSE: To evaluate the accuracy and inter-observer variability when CT angiography is used to identify unruptured intracranial aneurysm growth. METHODS: Two silicone phantom models were used in this study. Each phantom had eight aneurysms of variable size. The size and location of aneurysms in phantom 1 were representative of real patient aneurysms who presented to our institution. Phantom 2 contained aneurysms in the same locations, but with enlargement in various directions. Three blinded board-certified neuroradiologists were asked to identify the size of each aneurysm in three dimensions using CT angiography. The individual enlargement detection rates and inter-observer agreement rates of aneurysm enlargement among the three experts were calculated. RESULTS: The detection rate of aneurysm enlargement in one dimension was 58.3% among the three observers. Accurate detection of enlargement in all dimensions was 12.5% among the three observers. Detection accuracy was not related to the size of enlargement. Significant inter-observer measurement variability was present. CONCLUSION: The use of CT angiography was associated with a poor ability to identify aneurysm enlargementaccurately. Further human studies are required to confirm our findings.

Hemorrhage associated with ventriculoperitoneal shunt placement in aneurysmal subarachnoid hemorrhage patients on a regimen of dual antiplatelet therapy: a retrospective analysis.

OBJECTIVE: Intracranial stenting and flow diversion require the use of dual antiplatelet therapy (DAPT) to prevent in-stent thrombosis. DAPT may significantly increase the risk of hemorrhagic complications in patients who require subsequent surgical interventions. In this study, the authors sought to investigate whether DAPT is a risk factor for hemorrhagic complications associated with ventriculoperitoneal (VP) shunt placement in patients with aneurysmal subarachnoid hemorrhage (aSAH). Moreover, the authors sought to compare VP shunt complication rates with respect to the shunt's location from the initial external ventricular drain (EVD) site. METHODS: Patients with aSAH who presented to the authors' institution from July 2009 through November 2016 and required VP shunt placement for persistent hydrocephalus were included. The rates of hemorrhagic complications associated with VP shunt placement were compared between patients who were on a regimen of DAPT (aspirin and clopidogrel) for use of a stent or flow diverter, and patients who underwent microsurgical clipping or coiling only and were not on DAPT using a backward stepwise multivariate analysis. Rates of radiographic hemorrhage and infection-related VP shunt revision were compared between patients who underwent VP shunt placement along the same track and those who underwent VP shunt placement at a different site (contralateral or posterior) from the initial EVD. RESULTS: A total of 443 patients were admitted for the management of aSAH. Eighty of these patients eventually required VP shunt placement. Thirty-two patients (40%) had been treated with stent-assisted coiling or flow diverters and required DAPT, whereas 48 patients (60%) had been treated with coiling without stents or surgical clipping and were not on DAPT at the time of VP shunt placement. A total of 8 cases (10%) of new hemorrhage were observed along the intracranial proximal catheter of the VP shunt. Seven of these hemorrhages were observed in patients on DAPT, and 1 occurred in a patient not on DAPT. After multivariate analysis, only DAPT was significantly associated with hemorrhage (OR 31.23, 95% CI 2.98-327.32; p = 0.0001). One patient (3%) on DAPT who experienced hemorrhage required shunt revision for hemorrhage-associated proximal catheter blockage. The remaining 7 hemorrhages were clinically insignificant. The difference in rates of hemorrhage between shunt placement along the same track and placement at a different site of 0.07 was not significant (6/47 vs 2/32, p = 0.46). The difference in infection-related VP shunt revision rate was not significantly different (1/47 vs 3/32, p = 0.2978). CONCLUSIONS: This clinical series confirms that, in patients with ruptured aneurysms who are candidates for stent-assisted coiling or flow diversion, the risk of clinically significant VP shunt-associated hemorrhage with DAPT is low. In an era of evolving endovascular therapeutics, stenting or flow diversion is a viable option in select aSAH patients.

Plasma Soluble Human Elastin Fragments as an Intra-Aneurysmal Localized Biomarker for Ruptured Intracranial Aneurysm.

Background Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms. Methods and Results One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent-assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a microcatheter. The tip of the microcatheter was placed inside the aneurysm's sac in close proximity to the inner wall of the dome. Plasma levels of elastin fragments were measured using an ELISA -based method. Mean plasma level of soluble human elastin fragments was significantly greater in ruptured aneurysms when compared with nonruptured aneurysms (102.0±15.5 versus 39.3±9.6 ng/mL; P<0.001). Mean plasma level of soluble human elastin fragments did not have significant correlation with age, sex, size, or aneurysm location. Conclusions The present study revealed that a significantly higher concentration of soluble human elastin fragments in the lumen of ruptured intracranial aneurysms when compared with nonruptured ones.

Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: association with reduced risk of clinical vasospasm and delayed cerebral ischemia.

OBJECTIVE Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients. METHODS Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression. RESULTS Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097-0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01-0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9). CONCLUSIONS The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.