Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial.

Background: Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH. Methods: In this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation. Blood and cerebrospinal fluid (CSF) were collected to quantify inflammatory markers. Cerebral vasospasm severity and functional outcomes (modified Rankin Scale, mRS) were analyzed. Results: No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than sham (p < 0.001). In the taVNS group, TNF-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); IL-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%), with significant improvement from admission to first follow-up (p = 0.014), unlike the sham group (p = 0.18). The taVNS group had a significantly lower rate of discharge to skilled nursing facility or hospice (p = 0.04). Conclusion: taVNS is a non-invasive method of neuro- and systemic immunomodulation. This trial supports that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04557618.

A phase 1/2 study of disulfiram and copper with concurrent radiation therapy and temozolomide for patients with newly diagnosed glioblastoma.

BACKGROUND: This phase 1/2 study evaluates the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM). METHODS: Patients received standard RT and TMZ with DSF (250-375 mg daily) and Cu, followed by adjuvant TMZ plus DSF (500 mg/day) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry. RESULTS: Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wildtype cases. In the phase-1 arm, 18 patients were treated; dose-limiting toxicity (DLT) probabilities were 10% (95% CI: 3-29%) at 250 mg/day and 21% (95% CI: 7-42%) at 375 mg/day. The phase 2 arm treated 15 additional patients at 250 mg/day. No significant difference in overall survival or progression-free survival were noted between IDH-mutant and NF1-mutant cohorts compared to institutionally counterparts treated without DSF/Cu. However, extended remission occurred in three BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors. CONCLUSIONS: The maximum tolerated dose of DSF with RT and TMZ is 375 mg/day. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation.

Federal and foundational research funding trends for cerebrovascular neurosurgeons: the decline of the cerebrovascular surgeon-scientist?

OBJECTIVE: The number of cerebrovascular (CV) surgeons has grown with the rise of endovascular neurosurgery. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased. With increasing numbers of CV neurosurgeons in the US workforce, the authors analyzed associated changes in National Institutes of Health (NIH) and Neurosurgery Research and Education Foundation (NREF) funding trends for CV surgeons over time. METHODS: Publicly available data were collected on currently practicing academic CV surgeons in the US. Inflation-adjusted NIH funding between 2009 and 2021 was surveyed using NIH RePORTER and Blue Ridge Institute for Medical Research data. The K12 Neurosurgeon Research Career Development Program and NREF grant data were queried for CV-focused grants. Pearson R correlation, chi-square analysis, and the Mann-Whitney U-test were used for statistical analysis. RESULTS: From 2009 to 2021, NIH funding increased: in total (p = 0.0318), to neurosurgeons (p < 0.0001), to CV research projects (p < 0.0001), and to CV surgeons (p = 0.0018). During this time period, there has been an increase in the total number of CV surgeons (p < 0.0001), the number of NIH-funded CV surgeons (p = 0.0034), and the percentage of CV surgeons with NIH funding (p = 0.370). Additionally, active NIH grant dollars per CV surgeon (p = 0.0398) and the number of NIH grants per CV surgeon (p = 0.4257) have increased. Nevertheless, CV surgeons have been awarded a decreasing proportion of the overall pool of neurosurgeon-awarded NIH grants during this time period (p = 0.3095). In addition, there has been a significant decrease in the number of K08, K12, and K23 career development awards granted to CV surgeons during this time period (p = 0.0024). There was also a significant decline in the proportion of K12 (p = 0.0044) and downtrend in early-career NREF (p = 0.8978) grant applications and grants awarded during this time period. Finally, NIH-funded CV surgeons were more likely to have completed residency less recently (p = 0.001) and less likely to have completed an endovascular fellowship (p = 0.044) as compared with non-NIH-funded CV surgeons. CONCLUSIONS: The number of CV surgeons is increasing over time. While there has been a concomitant increase in the number of NIH-funded CV surgeons and the number of NIH grants awarded per CV surgeon in the past 12 years, there has also been a significant decrease in CV surgeons with K08, K12, and K23 career development awards and a downtrend in CV-focused K12 and early-career NREF applications and awarded grants. The latter findings suggest that the pipeline for future NIH-funded CV surgeons may be in decline.

The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study.

Introduction: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. 3,10,13 However, the effects of taVNS on cardiovascular dynamics in critically ill patients like those with SAH have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population 5 . Therefore, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study. Methods: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a Sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored rapidly responsive cardiovascular biomarkers in patients exhibiting clinical improvement. Results: We found that repetitive taVNS did not significantly alter heart rate, corrected QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity from 5-10 days after initial treatment, as compared to the sham treatment. Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, intracranial pressure, or heart rate variability. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than 1 point in their Modified Rankin Score at the time of discharge. Conclusions: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment. Trial registration: NCT04557618.

Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial.

Background: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints. Materials and methods: The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient's hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH. Discussion: Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH. Trial registration: Clinical Trials Registered, NCT04557618. Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Comparison between transradial and transfemoral mechanical thrombectomy for ICA and M1 occlusions: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: The role for the transradial approach for mechanical thrombectomy is controversial. We sought to compare transradial and transfemoral mechanical thrombectomy in a large multicenter database of acute ischemic stroke. METHODS: The prospectively maintained Stroke Thrombectomy and Aneurysm Registry (STAR) was reviewed for patients who underwent mechanical thrombectomy for an internal carotid artery (ICA) or middle cerebral artery M1 occlusion. Multivariate regression analyses were performed to assess outcomes including reperfusion time, symptomatic intracerebral hemorrhage (ICH), distal embolization, and functional outcomes. RESULTS: A total of 2258 cases, 1976 via the transfemoral approach and 282 via the transradial approach, were included. Radial access was associated with shorter reperfusion time (34.1 min vs 43.6 min, P=0.001) with similar rates of Thrombolysis in Cerebral Infarction (TICI) 2B or greater reperfusion (87.9% vs 88.1%, P=0.246). Patients treated via a transradial approach were more likely to achieve at least TICI 2C (59.6% vs 54.7%, P=0.001) and TICI 3 reperfusion (50.0% vs 46.2%, P=0.001), and had shorter lengths of stay (mean 9.2 days vs 10.2, P<0.001). Patients treated transradially had a lower rate of symptomatic ICH (8.0% vs 9.4%, P=0.047) but a higher rate of distal embolization (23.0% vs 7.1%, P<0.001). There were no significant differences in functional outcome at 90 days between the two groups. CONCLUSIONS: Radial and femoral thrombectomy resulted in similar clinical outcomes. In multivariate analysis, the radial approach had improved revascularization rates, fewer cases of symptomatic ICH, and faster reperfusion times, but higher rates of distal emboli. Further studies on the optimal approach are necessary based on patient and disease characteristics.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

In-hospital imaging utilization after elective endovascular brain aneurysm treatment: a surrogate metric for the value of hospitalization.

OBJECTIVE: Despite the adoption of same-day outpatient surgical procedures in some specialties, it remains common practice to admit patients for monitoring after elective endovascular treatment of brain aneurysms to monitor for complications. The necessity of such monitoring has not been fully characterized. Here, the authors reviewed the utilization of imaging during posttreatment hospitalization, a surrogate measure for workup of suspected complications requiring hospital resources, to infer the value of inpatient monitoring after endovascular aneurysm treatment. METHODS: Clinical and angiographic data from eligible patients were retrospectively assessed for demographic characteristics, imaging indications, timing of imaging, and imaging findings. Patients were included if they underwent elective endovascular brain aneurysm treatment, and patients were excluded if significant intraprocedural complications occurred. The recorded imaging modalities included CT, MRI, catheter-based imaging, and ultrasound; plain radiographs were excluded. Multivariable logistic regression analysis was performed to identify predictors of the need for posttreatment imaging. RESULTS: In total, 1229 elective endovascular procedures for brain aneurysm treatment were included. Patients underwent imaging before discharge in 13.4% (165/1229) of cases, with significant findings in 5.0% (61/1229) of cases. The median (interquartile range) time to first posttreatment imaging was 13.2 (4.2-22.8) hours. The need for imaging during posttreatment hospitalization was positively associated with larger aneurysm size (p < 0.05) and negatively associated with underlying cardiovascular disease (p < 0.05). CONCLUSIONS: More than 1 in 8 patients who underwent elective endovascular brain aneurysm treatment required imaging during posttreatment hospitalization, most within the first 24 hours, and 1 in 20 had significant findings. These results suggest the importance of short-term hospitalization after elective endovascular aneurysm treatment.

Outcomes of mechanical thrombectomy in stroke patients with extreme large infarction core.

BACKGROUND: Recent clinical trials have demonstrated that patients with large vessel occlusion (LVO) and large infarction core may still benefit from mechanical thrombectomy (MT). In this study, we evaluate outcomes of MT in LVO patients presenting with extremely large infarction core Alberta Stroke Program Early CT Score (ASPECTS 0-2). METHODS: Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) was interrogated. We identified thrombectomy patients presenting with an occlusion in the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery and extremely large infarction core (ASPECTS 0-2). A favorable outcome was defined by achieving a modified Rankin scale of 0-3 at 90 days post-MT. Successful recanalization was defined by achieving a modified Thrombolysis In Cerebral Ischemia (mTICI) score ≥2B. RESULTS: We identified 58 patients who presented with ASPECTS 0-2 and underwent MT . Median age was 70.0 (59.0-78.0) years, 45.1% were females, and 202 (36.3%) patients received intravenous tissue plasminogen activator. There was no difference regarding the location of the occlusion (p=0.57). Aspiration thrombectomy was performed in 268 (54.6%) patients and stent retriever was used in 70 (14.3%) patients. In patients presenting with ASPECTS 0-2 the mortality rate was 4.5%, 27.9% had mRS 0-3 at day 90, 66.67% ≥70 years of age had mRS of 5-6 at day 90. On multivariable analysis, age, National Institutes of Health Stroke Scale on admission, and successful recanalization (mTICI ≥2B) were independently associated with favorable outcomes. CONCLUSIONS: This multicentered, retrospective cohort study suggests that MT may be beneficial in a select group of patients with ASPECTS 0-2.

Comparative cost analysis of endovascular and open approaches for elective treatment of middle cerebral artery aneurysms.

BACKGROUND: Intracranial aneurysms of the middle cerebral artery can be treated using several open surgical and endovascular approaches. Given the growing evidence of clinical equipoise between these various treatment strategies, there is a need to assess the costs associated with each. METHODS: Cost of aneurysm treatment was divided into two categories for comparison. "Initial cost" comprised the total in-hospital expenses for initial aneurysm treatment and "total cost" comprised initial aneurysm treatment and all expenses relating to readmission due to treatment-related complications, prescribed catheter angiograms for monitoring of treatment stability, and any retreatments needed for a given aneurysm. The open surgical group was subdivided into a pterional approach group and a lateral supraorbital (LSO) approach group for. RESULTS: Median initial cost was $37,152 (IQR $31,318-$44,947) for aneurysms treated with the pterional approach, $29,452 (IQR $27,779-$32,826) for aneurysms treated with the LSO approach, and $19,587 (IQR $14,125-$30,521) for aneurysms treated with endovascular approaches. The median total cost was $39,737 (IQR $33,891-$62,259) for aneurysms treated with the pterional approach, $31,785 (IQR $29,513-$41,099) for aneurysms treated with the LSO approach, and $24,578 (IQR $18,977-$34,547) for aneurysms treated with endovascular approaches. Analysis of variance test demonstrated variance across groups for both initial and total cost (p = 0.004, p = 0.008, respectively). In our subsequent analysis, initial cost and total cost were higher in the pterional group than the endovascular group (p = 0.003 and p = 0.006, respectively). CONCLUSIONS: Endovascular treatment of elective aneurysms has a significantly lower cost than open surgical treatment with the pterional approach, but not with the LSO approach. For aneurysms not amenable to endovascular treatment, a minimally invasive LSO approach carries a lower cost burden than a pterional approach.

Natural history and growth rate of intracranial aneurysms in Loeys-Dietz syndrome: implications for treatment.

OBJECTIVE: Loeys-Dietz syndrome (LDS) is a heritable aortopathy associated with craniofacial abnormalities and dilatation and dissection of the aorta and its branches, as well as increased risk for intracranial aneurysms (ICAs). Given the rarity of the disease, the authors aimed to better define the natural history and role for the treatment for ICAs in these patients. METHODS: The medical records of 83 patients with LDS were retrospectively reviewed to obtain clinical and genetic history and vascular imaging of the aorta, aortic branches, and intracranial vessels. Serial radiology reports and cervical and intracranial vascular images were reviewed to determine presence, location, and size of ICAs. RESULTS: In total, 55 patients (66.3%) had at least two screening intracranial vascular examinations, and 19 (22.9%) had at least 1 ICA detected. Aneurysms were typically small (mean ± SD 3.2 ± 1.8 mm). ICAs were most often located in the cavernous carotid, followed by the ophthalmic and anterior cerebral artery vessels. The rate of ICA growth was 0.43 ± 0.53 mm/year, similar to that of the general population. Three patients underwent intervention for an ICA, with 1 procedure complicated by stroke and resulting in transient hemiparesis. Several illustrative cases detail the authors' experience with ICA growth, de novo aneurysm formation, and ICA intervention in this rare patient population. CONCLUSIONS: ICAs in patients with LDS are common, are frequently small, and have a growth rate similar to that of unruptured ICAs in the general population. More aggressive or earlier intervention for asymptomatic ICAs identified in LDS patients compared with the general population is likely unwarranted based on the authors' experience at their institution.

Comparison of balloon guide catheter versus non-balloon guide catheter for mechanical thrombectomy in patients with distal medium vessel occlusion.

BACKGROUND: Several studies have established the safety and efficacy of balloon guide catheters (BGCs) for large vessel occlusions. However, the utility of BGCs remains largely unexplored for distal medium vessel occlusions (DMVOs). In this study, we aim to compare the outcomes of BGC vs. Non-BGC in patients undergoing mechanical thrombectomy (MT) for DMVO. METHOD: This retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) encompassed adult patients with acute anterior cerebral artery, posterior cerebral artery, and middle cerebral artery-M2-3-4 occlusions. Procedure times, safety, recanalization, and neurological outcomes were compared between the two groups, with subgroup analysis based on first-line thrombectomy techniques. RESULTS: A total of 1508 patients were included, with 231 patients (15.3%) in the BGC group and 1277 patients (84.7%) in the non-BGC group. The BGC group had a lower modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2C (43.2% vs 52.7%, P=0.01), longer time from puncture to intracranial access (15 vs 8 min, P<0.01), and from puncture to final recanalization (97 vs 34 min, P<0.01). In the Solumbra subgroup, the first pass effect (FPE) rate was lower in the BGC group (17.4% vs 30.7%, P=0.03). Regarding clinical outcomes, the BGC group had a lower rate of distal embolization (8.8% vs 14.9%, P=0.03). CONCLUSION: Our study found that use of BGC in patients with DMVO was associated with lower mTICI scores, decreased FPE rates, reduced distal embolization, and longer procedure times.

Mechanical thrombectomy for the treatment of primary and secondary anterior cerebral artery occlusions: insights from STAR.

BACKGROUND: The safety and efficacy of mechanical thrombectomy (MT) for the treatment of acute anterior cerebral artery (ACA) occlusions have not clearly been delineated. Outcomes may be impacted based on whether the occlusion is isolated to the ACA (primary ACA occlusion) or occurs in conjunction with other cerebral arteries (secondary). METHODS: We performed a retrospective review of the multicenter Stroke Thrombectomy and Aneurysm (STAR) database. All patients with MT-treated primary or secondary ACA occlusions were included. Baseline characteristics, procedural outcomes, complications, and clinical outcomes were collected. Primary and secondary ACA occlusions were compared using the Mann-Whitney U test and Kruskal-Willis test for continuous variables and the χ2 test for categorical variables. RESULTS: The study cohort comprised 238 patients with ACA occlusions (49.2% female, median (SD) age 65.6 (16.7) years). The overall rate of successful recanalization was 75%, 90-day good functional outcome was 23%, and 90-day mortality was 35%. There were 44 patients with a primary ACA occlusion and 194 patients with a secondary ACA occlusion. When adjusted for baseline variables, the rates of successful recanalization (68% vs 76%, P=0.27), 90-day good functional outcome (41% vs 19%, P=0.38), and mortality at 90 days (25% vs 38%, P=0.12) did not differ between primary and secondary ACA occlusion groups. CONCLUSION: Clinical and procedural outcomes are similar between MT-treated primary and secondary ACA occlusions for select patients. Our findings demonstrate the need for established criteria to determine ideal patient and ACA stroke characteristics amenable to MT treatment.

Stability of navigation in catheter-based endovascular procedures.

Endovascular procedures provide surgeons and other interventionalists with minimally invasive methods to treat vascular diseases by passing guidewires, catheters, sheaths and treatment devices into the vasculature to and navigate toward a treatment site. The efficiency of this navigation affects patient outcomes, but is frequently compromised by catheter "herniation", in which the catheter-guidewire system bulges out from the intended endovascular pathway so that the interventionalist can no longer advance it. Here, we showed herniation to be a bifurcation phenomenon that can be predicted and controlled using mechanical characterizations of catheter-guidewire systems and patientspecific clinical imaging. We demonstrated our approach in laboratory models and, retrospectively, in patients who underwent procedures involving transradial neurovascular procedures with an endovascular pathway from the wrist, up in the arm, around the aortic arch, and into the neurovasculature. Our analyses identified a mathematical navigation stability criterion that predicted herniation in all of these settings. Results show that herniation can be predicted through bifurcation analysis, and provide a framework for selecting catheter-guidewire systems to avoid herniation in specific patient anatomy.

Need for Y-stenting in stent-assisted coiling of wide-neck bifurcation aneurysms.

BACKGROUND AND PURPOSE: Stent-assisted coiling of wide neck bifurcation aneurysms in the anterior communicating segment and basilar tip region can be performed with varying stent configurations, including single stenting or Y-stenting. Y-stenting requires two stents and thus incurs greater cost and procedural complexity than single-stent constructs. The influence of first stent type on the need for Y-stenting remains unknown. MATERIALS AND METHODS: Clinical and angiographic data were retrospectively obtained for patients that underwent stent-assisted coiling for basilar tip or anterior communicating aneurysms at a high-volume center. Patients were included in this study if stent-assisted coiling was performed using Neuroform Atlas or LVIS Jr stents. A multivariate binary logistic regression was performed to measure the influence of first stent type on the need for Y-stenting. RESULTS: Stent-assisted coiling was used to treat 82 aneurysms in 81 patients during the study period, and Y-stenting was performed in 18.3% (15/82) of cases. In multivariate logistic regression analysis, use of LVIS Jr. as the first stent did not significantly influence the need for subsequent Y-stenting after controlling for aneurysm morphology (OR 0.65, 95% CI 0.18-2.43). CONCLUSION: Controlling for aneurysm morphology and location, the use of Y-stenting for stent-assisted coiling was not independently influenced by the choice of LVIS Jr or Neuroform Atlas as the first stent. A larger cohort may reveal differences between these two stents, particularly for aneurysms with large neck sizes.

A review of technological innovations leading to modern endovascular brain aneurysm treatment.

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment.

Early Brain Injury After Subarachnoid Hemorrhage: Incidence and Mechanisms.

Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.

Effect of intravenous thrombolysis before endovascular therapy on outcomes in patients with large core infarct.

BACKGROUND: The safety and efficacy of bridging therapy with intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in patients with large core infarct has not been sufficiently studied. In this study, we compared the efficacy and safety outcomes between patients who received IVT+MT and those treated with MT alone. METHODS: This is a retrospective analysis of the Stroke Thrombectomy Aneurysm Registry (STAR). Patients with Alberta Stroke Program Early CT Score (ASPECTS) ≤5 treated with MT were included in this study. Patients were divided into two groups based on pre-treatment IVT (IVT, no IVT). Propensity score matched analysis were used to compare outcomes between groups. RESULTS: A total of 398 patients were included; 113 pairs were generated using propensity score matching analyses. Baseline characteristics were well balanced in the matched cohort. The rate of any intracerebral hemorrhage (ICH) was similar between groups in both the full cohort (41.4% vs 42.3%, P=0.85) and matched cohort (38.55% vs 42.1%, P=0.593). Similarly, the rate of significant ICH was similar between the groups (full cohort: 13.1% vs 16.9%, P=0.306; matched cohort: 15.6% vs 18.95, P=0.52). There was no difference in favorable outcome (90-day modified Rankin Scale 0-2) or successful reperfusion between groups. In an adjusted analysis, IVT was not associated with any of the outcomes. CONCLUSION: Pretreatment IVT was not associated with an increased risk of hemorrhage in patients with large core infarct treated with MT. Future studies are needed to assess the safety and efficacy of bridging therapy in patients with large core infarct.

Risk factors and predictors of intracranial hemorrhage after mechanical thrombectomy in acute ischemic stroke: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: Reducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy. METHODS: This is a retrospective review of the Stroke Thrombectomy and Aneurysm Registry (STAR) database. All patients who underwent AIS thrombectomy with available ICH data were included. Multivariable regression models were developed to identify predictors of ICH after thrombectomy. Subgroup analyses were performed stratified by symptom status and European Cooperative Acute Stroke Study (ECASS) grade. RESULTS: The study cohort comprised 6860 patients. Any ICH and symptomatic ICH (sICH) occurred in 25% and 7% of patients, respectively. Hemorrhagic infarction 1 (HI1) occurred in 36%, HI2 in 24%, parenchymal hemorrhage 1 (PH1) in 22%, and PH2 in 17% of patients classified by ECASS grade. Intraprocedural complications independently predicted any ICH (OR 3.8083, P<0.0001), PH1 (OR 1.9053, P=0.0195), and PH2 (OR 2.7347, P=0.0004). Race also independently predicted any ICH (black: OR 0.5180, P=0.0017; Hispanic: OR 0.4615, P=0.0148), sICH (non-white: OR 0.4349, P=0.0107), PH1 (non-white: OR 3.1668, P<0.0001), and PH2 (non-white: OR 1.8689, P=0.0176), with white as the reference. Primary mechanical thrombectomy technique also independently predicted ICH. ADAPT (A Direct Aspiration First Pass Technique) was a negative predictor of sICH (OR 0.2501, P<0.0001), with stent retriever as the reference. CONCLUSIONS: This study identified ICH risk factors after AIS thrombectomy using real-world data. There was a propensity towards a reduced sICH risk with direct aspiration. Procedural complications and ethnicity were predictors congruent between categories of any ICH, sICH, PH1, and PH2. Further investigation of technique and ethnicity effects on ICH and outcomes after AIS thrombectomy is warranted.