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Woven EndoBridge (WEB) Devices area recent tool in endovascular cerebralaneurysm repair, proposed as areplacement for Stent-Assisted Coiling(SAC). Still a new technology, they were FDAapproved in 2019. WEB devices are ~$15K per device, leading to questions about the costeffectiveness. (Stents cost anywherefrom 7K-13K, and coils cost ~2K-5Kper, but typically use multiples.)

This report introduces a novel surgical technique for middle meningeal artery embolization (MMAE) during a mini-craniotomy for subdural hematoma (SDH) evacuation. A patient with multiple health issues presented with a 14 mm right subacute SDH. During surgery, the MMA was retrogradely catheterized and embolized using Onyx 18. This approach, combining MMAE with hematoma evacuation, resulted in successful resolution of the SDH without complications. The procedure offers a more efficient workflow by integrating 2 interventions into 1, potentially reducing recurrence rates of SDH.

Background: A 49-year-old woman with a history of hypertension presented to the emergency department with right eye redness, proptosis, orbital fullness, and blurry vision. She had initially been diagnosed with an orbital pseudotumor, and the symptoms worsened over a course of steroids. Computed tomography angiography raised concern for a carotid-cavernous fistula (CCF), which was subsequently confirmed by digital subtraction angiography., Observations: She underwent fistula coil embolization via the internal maxillary artery and inferior ophthalmic vein (IOV). At the 2-month follow-up, she reported complete resolution of diplopia, orbital fullness, and proptosis. An ophthalmology examination revealed normal visual fields bilaterally., Lessons: CCF embolization is rarely performed through the IOV, with only 5 reported cases in the literature. This case demonstrates that the procedure can be easily performed if the anatomy is favorable over the superior ophthalmic vein, with the illustration of good cosmetic outcomes. https://thejns.org/doi/10.3171/CASE24183.

Background: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography., Methods: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA)., Results: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy)., Conclusions: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice., Competing Interests: Competing interests: ST previously consulted for Corindus Vascular Robotics in 2018 and 2019 but currently has no relationship or stock options with the company. BW was a consultant for Siemens/Corindus in 2020 but currently has no relationship or stock options with the company., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Importance: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process., Methods: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]., Conclusion: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Robotic-assisted carotid artery angioplasty and stenting is becoming more popular due to its precision and radiation safety. In this video, we present a case using the CorPath GRX Robotic System (Corindus, a Seimens Healthineers Company, Waltham, Massachusetts, USA) with step-by-step procedure process and technical nuances (video 1). We demonstrate that cervical carotid angioplasty and stenting can be safely performed using the robotic system with efficiency and accuracy., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bullet embolism after high velocity penetrating trauma is a rare event that can have devastating and wide-ranging effects distant from the original site of injury. A 29-year-old presented with multiple gunshot wounds to the chest, back, abdomen, and lower extremities but no penetrating head injury. After proper resuscitation, the patient was noted to have left-sided hemiparesis and computed tomography angiography of the head showed a bullet fragment that had traveled to the right M1 segment of the middle cerebral artery resulting in occlusion of the vessel. Mechanical thrombectomy was performed in an attempt to remove the bullet fragment but this was unsuccessful as the fragment was firmly lodged in the blood vessel. Aspiration of clot distal to the fragment was then performed in hopes of preventing a large volume ischemic event which was angiographically successful resulting in TICI 2c revascularization. This case demonstrates that thrombectomy can be safely and successfully performed distal to a lodged foreign body., Competing Interests: Declaration of conflicting interestsBranden Cord, MD PhD reports consulting fees from Stryker, QApel, Penumbra, and Silk Road. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Clipping of basilar tip aneurysms presents unique challenges due to the risk of perforator compromise and subsequent disabling stroke., Method: Herein, we describe the correct trajectory of the clip applier to clip basilar tip aneurysms through an orbitozygomatic approach to prevent perforator injury and discuss management of intraoperative neuromonitoring changes., Conclusion: We anticipate that this video and illustration will aid surgeons as they treat complex wide-necked basilar tip aneurysms with microsurgical clipping., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The mechanisms of cognitive decline after intraventricular hemorrhage (IVH) in some patients continue to be poorly understood. Multiple rodent models of intraventricular or subarachnoid hemorrhage have only shown mild or even no cognitive impairment on subsequent behavioral testing. In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most significantly activated signaling pathway was the classical complement pathway, which is used by microglia to remove synapses, followed by activation of the Fc receptor and DAP12 pathways. Thus, our study lays the groundwork for identifying signaling pathways that could be targeted to ameliorate behavioral deficits after IVH., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background  Supraorbital eyebrow craniotomy is a minimally invasive alternative to a frontotemporal craniotomy and is often used for tumor and vascular pathologies. The purpose of this study was to investigate how patient cosmetic outcomes are affected by technique variations of this approach. Methods  PubMed, Embase, and Scopus databases were systematically searched, and results were reported according to PRISMA guidelines. For the meta-analysis portion, the DerSimonian-Laird random effects model was used, and the primary end points were patient satisfaction and percentage of permanent cosmetic complications. Results  A total of 2,629 manuscripts were identified. Of those, 124 studies (8,241 surgical cases) met the inclusion criteria. Overall, 93.04 ± 11.93% of patients reported favorable cosmetic outcome following supraorbital craniotomy, and mean number of cases with permanent cosmetic complications was 6.62 ± 12.53%. We found that vascular cases are associated with more favorable cosmetic outcomes than tumor cases ( p  = 0.0001). Addition of orbital osteotomy or use of a drain is associated with adverse cosmetic outcomes ( p  = 0.001 and p  = 0.0001, respectively). The location of incision, size of craniotomy, utilization of an endoscope, method of cranial reconstruction, skin closure, use of antibiotics, and addition of pressure dressing did not significantly impact cosmetic outcomes ( p  > 0.05 for all). Conclusions  Supraorbital craniotomy is a minimally invasive technique associated with generally high favorable cosmetic outcomes. While certain techniques used in supraorbital keyhole approach do not pose significant cosmetic risks, utilization of an orbital osteotomy and the addition of a drain correlate with unfavorable cosmetic outcomes., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Mechanisms underlying memory and cognitive dysfunction following spontaneous intracranial hemorrhage are diverse. The aim of this systematic review was to provide a contemporary review of the commonly reported mechanisms responsible for memory impairment following nontraumatic intracranial hemorrhage. PubMed, Embase, and Scopus databases were systematically searched for pre-clinical studies, and results were reported according to PRISMA guidelines. Methodological quality assessment was performed according to the SYRCLE's Risk of Bias tool. Ninety studies met the inclusion criteria. Most of animal studies reported on subarachnoid hemorrhage (48%), followed by intraparenchymal hemorrhage (44%), and intraventricular hemorrhage (8%). Most of subarachnoid hemorrhage studies (30%) reported neuronal apoptosis as a mechanism for memory dysfunction, whereas the most commonly described mechanism following intraparenchymal hemorrhage (40%) and intraventricular hemorrhage (23%) was a proinflammatory response. Based on SYRCLE's Risk of Bias assessment, the average methodological risk of bias of all studies was 56.83 ± 12.77% on a 0-100% scale. There is a great need not only for more preclinical studies with improved methodology, but also for studies reporting negative treatment effects and for multicenter animal studies. In vivo studies on non-rodent animal ICH models can also be helpful., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objective: Although delayed postoperative clip slippage has been reported in previous case reports and case series, its true incidence with high rate of follow-up imaging has not been reported. We attempted to determine the incidence of clip slippage in a cohort of consecutive aneurysm clippings., Methods: We performed a retrospective review of a prospectively maintained database of 115 consecutive saccular aneurysm clippings at a single institution. Postoperative imaging was reviewed for clip slippage within 24 hours and at 3-12 months. Eighty-six aneurysms (75.8%) were exclusively clipped with Sugitaclip (Mizuho Medical, Tokyo, Japan) Titanium II clips, 16 aneurysms were exclusively clipped with Yaşargil (Aesculap, Center Valley, PA) titanium clips (13.9%), 5 aneurysms were only clipped with Sugita aneurysm clips (4.3%), and 3 aneurysms were only clipped with Peter Lazic (Peter Lazic Microsurgical Innovations, Tuttlingen, Germany) clips (2.6%)., Results: In this cohort, 94.7% of clipped aneurysms had follow-up imaging within 24 hours, and 51.3% had delayed follow-up imaging within 3-12 months. We identified 3 cases of clip slippage in 115 consecutive aneurysm clippings, resulting in an incidence of 2.6%. The average cumulative closing force of clips per aneurysm across the study was 2.32 N, and the median number of clips placed was 1. Two of the 3 cases of clip slippage had a closing force <2.32 N and only placement of a single clip., Conclusions: Because our series showed a 2.6% incidence of clip slippage, clipped aneurysms should be monitored with early and delayed vascular follow-up imaging. Lower cumulative clip closing force, single clip placement, and oversized clip blade length may be risk factors for postoperative aneurysmal clip slippage., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Survivors of intraventricular hemorrhage are often left with significant long-term memory impairment; thus, research utilizing intraventricular hemorrhage animal models is essential. In this study, we sought out ways to measure intracranial pressure, mean arterial pressure, and cerebral perfusion pressure during nontraumatic intraventricular hemorrhage in rodents. The experimental design included three Sprague Dawley groups: sham, standard 200 µl intraventricular hemorrhage, and vehicle control groups. By introducing an intraparenchymal fiberoptic pressure sensor, precise intracranial pressure measurements were obtained in all groups. Cerebral perfusion pressures were calculated with the knowledge of intracranial pressure and mean arterial pressure values. As expected, the intraventricular hemorrhage and vehicle control groups both experienced a rise in the intracranial pressure and subsequent decline in cerebral perfusion pressure during intraventricular injection of autologous blood and artificial cerebrospinal fluid, respectively. The addition of an intraparenchymal fiberoptic pressure sensor is beneficial in monitoring precise intracranial pressure changes.

Background: Supraorbital eyebrow keyhole craniotomy is a minimally invasive alternative to a frontotemporal craniotomy and is often used for tumor resection and aneurysm clipping. The purpose of this study is to provide a contemporary review on the outcomes related to this approach and to determine whether they vary with the type of pathology and the addition of an endoscope., Methods: PubMed, Embase, and Scopus databases were systematically searched, and results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the meta-analysis portion, the DerSimonian-Laird random effects model was used., Results: A total of 2629 manuscripts were identified. of those, 124 studies (8241 surgical cases) met the inclusion criteria. Mean total complication rate was 26.7 ± 25.7% and the mean approach-related mortality rate was 1.3 ± 2.8%. Technical success, defined as gross total tumor resection or complete aneurysm clipping, was achieved in 83.6 ± 21.5% of the cases. Vascular pathologies were associated with greater technical success, lower total complications, and longer length of hospital stay compared with tumor cases (P < 0.05 for all). For vascular cases, addition of the endoscope yielded lower technical success (P = 0.001) and lower complication rate (P = 0.041). The use of the endoscope for tumor pathologies did not affect technical success, complications, mortality, length of hospital stay, operative time, or reoperation rate (P > 0.05)., Conclusions: The supraorbital craniotomy via an eyebrow incision is a feasible minimally invasive approach with an overall high technical success rate for both vascular and tumor pathologies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Limited data exists on the long-term effects of aneurysmal subarachnoid hemorrhage (SAH) on spatial memory. Herein, we used a computerized virtual water maze to evaluate the feasibility of spatial memory testing in pilot cohort of ten patients who survived previous SAH., Methods: Ten SAH survivors (5.8 ± 5.1 years after initial hemorrhage) and 7 age-matched controls underwent testing in a virtual water maze computer program. Additional subgroup analyses were performed to evaluate spatial reference memory correlation for ventricular size on admission, placement of an external ventricular drain and placement of a shunt., Results: With respect to the spatial memory acquisition phase, there was no significant difference of pathway length traveled to reach the platform between SAH survivors and control subjects. During the probe trial, control subjects spent significantly longer time in target quadrants compared to SAH survivors (F (3, 24) = 10.32, p = 0.0001; Target vs. Right: Mean percent difference 0.16 [0-0.32], p = 0.045; Target vs. Across: Mean percent difference 0.35 [0.19-0.51], p < 0.0001; Target vs. Left: Mean percent difference 0.21 [0.05-0.37], p = 0.0094). Furthermore, patients who initially presented with smaller ventricles performed worse that those patients who had ventriculomegaly and/or required surgical management of hydrocephalus., Conclusions: Our data demonstrate that SAH survivors have persistent spatial reference memory deficits years after the hemorrhage. Hydrocephalus at presentation and external ventricular drainage were not found to be associated with poor spatial memory outcomes in this pilot cohort. Therefore, other causes such as global cerebral edema or magnitude of initial ICP spike, need to be considered to be examined as root cause as well in subsequent studies. The protocol described in this manuscript is able to demonstrate a spatial reference memory deficit and can be used to study risk factors for spatial memory impairment on a larger scale., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Aneurysmal subarachnoid hemorrhage (SAH) is the most common cause of nontraumatic SAH. Current guidelines generally recommend observation for unruptured intracranial aneurysms smaller than 7 mm, for those are considered at low risk for spontaneous rupture according to available scoring systems., Objective: We observed a tendency for SAH in small intracranial aneurysms in patients who are methamphetamine users. A retrospective, single center study to characterize the size and location of ruptured and unruptured intracranial aneurysms in methamphetamine users was performed., Materials and Methods: Clinical characteristics and patient data were collected via retrospective chart review of patients with intracranial aneurysms and a history of methamphetamine use with a specific focus on aneurysm size and location., Results: A total of 62 patients were identified with at least one intracranial aneurysm and a history of methamphetamine use, yielding 73 intracranial aneurysms (n = 73). The mean largest diameter of unruptured aneurysms (n = 44) was 5.1 mm (median 4.5, SD 2.5 mm), smaller than for ruptured aneurysms (n = 29) with a mean diameter of 6.3 mm (median 5.5, SD 2.5 mm). Aneurysms measuring less than 7 mm presented with SAH in 36.5%. With regard to location, 28% (n = 42) of anterior circulation aneurysms less than 7 mm presented with rupture, in contrast to 70% (n = 10) of posterior circulation aneurysms which were found to be ruptured., Conclusions: Methamphetamine use may be considered a significant risk factor for aneurysmal SAH at a smaller aneurysm size than for other patients. These patients may benefit from a lower threshold for intervention and/or aggressive imaging and clinical follow-up.

Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Transradial access has recently been gaining more popularity in various neurointerventional procedures. To this day, a systematic review and meta-analysis investigating the outcomes of transradial access for mechanical thrombectomy in acute stroke have not been performed., Methods: PubMed, Embase, and Scopus databases were systematically searched. Studies published in the last ten years reporting on the use of transradial access for acute stroke intervention were eligible. The DerSimonian-Laird random effects model was used, and the primary endpoints included puncture to reperfusion time, end mRS, TICI reperfusion, mortality, and access site complications., Results: A total of 515 records were identified. Fourteen observational studies reported on the use of radial access for thrombectomy, with 10 of these studies (n = 309) included in the meta-analysis. Mean puncture to reperfusion time associated with the transradial access was 46.864 ± 6.601 min. Favorable end mRS of ≤ 2 was reported in 37.1 % ± 7.3 % of patients. TICI ≥ 2B was achieved in 84.6 % ± 3.4 % of patients. All-cause mortality was observed in 9.3 % ± 4.8 % of patients. Transradial access had low complications with only 1.4 % ± 0.7 % of stroke cases. When the transradial studies were compared to the contemporary randomized clinical trials using the standard transfemoral access, no significant differences were found in all of these primary outcomes., Conclusion: This meta-analysis study demonstrates that transradial access for mechanical thrombectomy in acute stroke may be a feasible and safe alternative. Future prospective studies are needed to validate these results., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Endovascular treatment is the mainstay therapy for brain aneurysms. About 15% of patients need re-treatment within six months due to early recanalization. In this study, we investigate risk factors associated with treatment failure., Methods: This retrospective cohort study includes endovascularly treated aneurysm cases between July 2012 and December 2015 at the University of California Davis Medical Center with pre-treatment and early post-treatment imaging. Thin cut 3D aneurysm volume rendering was used for morphologic analyses. Univariate and bivariate analyses were conducted to evaluate differences between patients and clinical factors by treatment failure., Results: Of the 50 patients who met the inclusion criteria, 41 (82.0%) were female, with an average age of 61 years. Most aneurysms were on the anterior communicating artery (40%) or posterior communicating artery (22.0%), and 34 (68%) aneurysms were ruptured. Early treatment failure was observed in 14 (28.0%) of endovascularly treated patients. Raymond-Roy class (RRC) was significantly associated with treatment failure (p = 0.0052), with 10 out of the 14 cases (71.4%) with early recanalization having an RRC of 3. Coil packing density did not associate with aneurysm recanalization (p = 0.61)., Conclusion: In our single institution series, patient characteristics, aneurysm characteristics, or coil packing density did not affect early aneurysm recanalization. RRC was the best predictor of early recanalization; however, further confirmation with additional studies are required. Although this study focused on early treatment failure, late recanalization has been shown with longer follow up. Further investigation into factors associated with late treatment failure will need further investigation. New intrasaccular devices and flow diverters will also likely play a role in reducing recurrence in the future as these treatments gain usage., (© 2020 Published by Elsevier Ltd.)

Background: Though there are many biomarker studies of plasma and serum in patients with aneurysmal subarachnoid hemorrhage (SAH), few have examined blood cells that might contribute to vasospasm. In this study, we evaluated inflammatory and prothrombotic pathways by examining mRNA expression in whole blood of SAH patients with and without vasospasm., Methods: Adult SAH patients with vasospasm (n = 29) and without vasospasm (n = 21) were matched for sex, race/ethnicity, and aneurysm treatment method. Diagnosis of vasospasm was made by angiography. mRNA expression was measured by Affymetrix Human Exon 1.0 ST Arrays. SAH patients with vasospasm were compared to those without vasospasm by ANCOVA to identify differential gene, exon, and alternatively spliced transcript expression. Analyses were adjusted for age, batch, and time of blood draw after SAH., Results: At the gene level, there were 259 differentially expressed genes between SAH patients with vasospasm compared to patients without (false discovery rate < 0.05, |fold change| ≥ 1.2). At the exon level, 1210 exons representing 1093 genes were differentially regulated between the two groups (P < 0.005, ≥ 1.2 |fold change|). Principal components analysis segregated SAH patients with and without vasospasm. Signaling pathways for the 1093 vasospasm-related genes included adrenergic, P2Y, ET-1, NO, sildenafil, renin-angiotensin, thrombin, CCR3, CXCR4, MIF, fMLP, PKA, PKC, CRH, PPARα/RXRα, and calcium. Genes predicted to be alternatively spliced included IL23A, RSU1, PAQR6, and TRIP6., Conclusions: This is the first study to demonstrate that mRNA expression in whole blood distinguishes SAH patients with vasospasm from those without vasospasm and supports a role of coagulation and immune systems in vasospasm.

Background: Blister aneurysms are a rare subclass of aneurysms, which remain challenging to treat both with open cerebrovascular and endovascular techniques, and clinicians continue to see poor outcomes in some cases despite improvements in technology. Based on our clinical observations, we hypothesized that patients with a Fisher grade 3 subarachnoid hemorrhage (SAH) from a ruptured anterior circulation blister aneurysm are significantly more likely to develop poor outcome due to delayed cerebral ischemia than patients with a Fisher grade 3 SAH from a ruptured anterior circulation saccular aneurysm., Methods: In this consecutive case series, we reviewed management, outcomes, and rates of delayed cerebral ischemia for all ruptured anterior circulation blister aneurysms from 2012 to 2018 at our institution and compared them to a concurrent cohort of ruptured saccular anterior circulation aneurysms. A blister aneurysm was defined as an aneurysm that arises from a nonbranching point and demonstrates hemispherical anatomy on diagnostic angiography., Results: We identified 14 consecutive ruptured anterior circulation blister aneurysms. Thirteen aneurysms were treated operatively- 5 with clip remodeling and 8 with flow diversion embolization. While clip remodeling had a high intraoperative rupture rate (80%), there was only one (12.5%) intraoperative rupture with flow diversion embolization. Outcomes were worsened by delayed cerebral ischemia from vasospasm in patients with Fisher 3 hemorrhages from blister aneurysms (86%). The rate of delayed cerebral ischemia from vasospasm was significantly higher for ruptured blister aneurysms than for a concurrent cohort of ruptured saccular aneurysms (8.6%, P = 0.0001)., Conclusion: Ruptured Fisher grade 3 anterior circulation blister aneurysms have a significantly higher incidence of delayed cerebral ischemia from vasospasm compared to saccular aneurysms, regardless of the treatment modality., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Brain Circulation.)

Neurobehavioral studies have produced contradictory findings concerning the function of neurogenesis in the adult dentate gyrus. Previous studies have proved inconsistent across several behavioral endpoints thought to be dependent on dentate neurogenesis, including memory acquisition, short-term and long-term retention of memory, pattern separation, and reversal learning. We hypothesized that the main function of dentate neurogenesis is long-term memory formation because we assumed that a newly formed and integrated neuron would have a long-term impact on the local neural network. We used a cyclin D2-knock-out (cyclin D2 -/- ) mouse model of endogenously deficient dentate neurogenesis to test this hypothesis. We found that cyclin D2 -/- mice had robust and sustained loss of long-term memory in two separate behavioral tasks, Morris water maze (MWM) and touchscreen intermediate pattern separation. Moreover, after adjusting for differences in brain volumes determined by magnetic resonance (MR) imaging, reduced dentate neurogenesis moderately correlated with deficits in memory retention after 24 hours. Importantly, cyclin D2 -/- mice did not show deficits in learning acquisition in a touchscreen paradigm of intermediate pattern separation or MWM platform location, indicating intact short-term memory. Further evaluation of cyclin D2 -/- mice is necessary to confirm that deficits are specifically linked to dentate gyrus neurogenesis since cyclin D2 -/- mice also have a reduced size of the olfactory bulb, hippocampus, cerebellum and cortex besides reduced dentate gyrus neurogenesis.

Our group has recently created a novel in-vivo human brain organoid vascularized with human iPSC-derived endothelial cells. In this review article, we discuss the challenges of creating a perfused human brain organoid model in an immunosuppressed rodent host and discuss potential applications for neurosurgical disease modeling.

Introduction: There continues to be a need to create an artificial human blood-brain barrier for pharmacological testing and modeling of diseases. Our group has recently vascularized human brain organoids with human iPSC-derived endothelial cells. Other groups have achieved brain organoid perfusion after vascularization with murine endothelial cells. Areas covered: This review article discusses the remaining hurdles, advantages, and limitations of creating a human organoid blood-brain barrier in rodents for novel drug discovery. Expert opinion: The creation of a human organoid blood-brain barrier in rodents will be feasible with appropriate molecular and cellular cues. An artificial human blood-brain barrier model may be used for pharmacological testing or for the study of the human blood-brain barrier in development or disease. Potential limitations of the model include an inferior competence of the blood-brain organoid barrier, the immunodeficient environment and low reproducibility due to variations in organoid morphology and vascularization. Despite its limitations, an artificial human blood-brain barrier model in rodents will further our understanding of blood-brain barrier pharmacology, and the field is expected to see significant advances in the next years.

The aim of this study was to vascularize brain organoids with a patient's own endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis patient were grown into whole-brain organoids. Simultaneously, iPSCs from the same patient were differentiated into ECs. On day 34, the organoid was re-embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro for 3-5 weeks or transplanted into immunodeficient mice on day 54, and animals were perfused on day 68. Coating of brain organoids on day 34 with ECs led to robust vascularization of the organoid after 3-5 weeks in vitro and 2 weeks in vivo. Human CD31-positive blood vessels were found inside and in-between rosettes within the center of the organoid after transplantation. Vascularization of brain organoids with a patient's own iPSC-derived ECs is technically feasible.

The accuracy of 3D time of Flight Magnetic Resonance Angiography (TOF MRA) has been studied extensively for following coiled intracranial aneurysms. It is used by many clinicians for non-invasive follow-up because of its adequate sensitivity in predicting aneurysmal recanalization compared to diagnostic cerebral angiography. The data on the accuracy of 3D TOF MRA for the Pipeline™ Embolization Device (PED) are sparse. In a retrospective chart review, we compared the accuracy of 3D TOF MRA of PED to coil embolization at our institution. 3D TOF MRA had a lower sensitivity and positive predictive value in detecting aneurysmal filling in PED-treated versus coiled aneurysms (57% versus 87% and 80% versus 100%, respectively). Analysis of discrepancies between conventional diagnostic angiography and 3D TOF MRA revealed that 3D TOF MRA was inaccurate in the setting of small residual necks and slow residual filling of the dome with fluid-fluid layers. Therefore, contrasted studies such as contrast-enhanced MRA may be preferred for non-invasively following PED-treated aneurysms to increase accuracy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Intraventricular hemorrhage causes spatial memory loss, but the mechanism remains unknown. Our recent studies demonstrated that traumatic brain injury activates Src family kinases, which cause spatial memory loss. To test whether the spatial memory loss was due to blood in the ventricles, which activated Src family kinases, we infused autologous whole blood or thrombin into the lateral ventricles of adult rats to model non-traumatic intraventricular hemorrhage. Hippocampal neuron loss was examined 1 day to 5 weeks later. Spatial memory function was assessed 29 to 33 days later using the Morris water maze. Five weeks after the ventricular injections of blood or thrombin, there was death of most hippocampal neurons and significant memory deficits compared with sham operated controls. These data show that intraventricular thrombin is sufficient to kill hippocampal neurons and produce spatial memory loss. In addition, systemic administration of the non-specific Src family kinase inhibitor PP2 or intraventricular injection of siRNA-Fyn, a Src family kinase family member, prevented hippocampal neuronal loss and spatial memory deficits following intraventricular hemorrhage. The data support the conclusions that thrombin mediates the hippocampal neuronal cell death and spatial memory deficits produced by intraventricular blood and that these can be blocked by non-specific inhibition of Src family kinases or by inhibiting Fyn.

Background: Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke with a variable presentation, ranging from headaches, to coma and death. Although the American Stroke Association has developed guidelines for the treatment of CVST, data are sparse on the outcome after treatment with anticoagulation, thrombolysis, and thrombectomy., Methods: In this retrospective review, we describe the 5-year UC Davis experience with spontaneous CVST., Results: Forty-one patients (mean age 37.5±23.1, range 0-96 years; 29 female) were identified with CVST. The majority of cases involved the transverse sinus (75.6%), sigmoid sinus (58.5%), and superior sagittal sinus (29.3%). The most common form of treatment was anticoagulation or antiplatelet therapy (n=35), while six patients were managed by observation alone. The overall 1-year modified Rankin score (mRS) was 1.4±1.5. Male patients and patients with a poor admission mRS had a worse outcome. Outcome was unaffected by hypercoagulable state, number of dural sinuses involved, the presence of intracranial hemorrhage, or seizures. Two patients who underwent anticoagulation therapy also required endovascular thrombectomy; both patients had a 1-year mRS of ≤2. Two patients underwent direct open surgical canalization of the superior sagittal sinus with varying outcomes (mRS 2 vs mRS 6)., Conclusions: In our series, the majority (92.9%) of patients with spontaneous dural sinus thrombosis had a favorable clinical outcome as defined by a mRS ≤2. Further prospective studies are needed to study the impact of anticoagulation on the clinical course of the disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Vascular trauma is associated with blunt skull base fractures and penetrating injuries. We review the contemporary management of cranial vascular trauma, including blunt and penetrating cerebrovascular injury as well as refractory epistaxis from facial trauma.

Posterior communicating artery (PCOM) aneurysms may cause third nerve palsies. The optimal treatment with clipping versus coiling remains controversial. Here we report on two cases of resolution of third nerve palsy after flow diversion embolization of large and giant PCOM aneurysms without adjuvant coil placement. The resolution of third nerve palsy was not preceded by significant shrinkage of the aneurysmal sac on MRI. However, one patient showed resolution of T2-weighted signal abnormalities in the midbrain and mesial temporal lobe despite a similar size of the aneurysm. Therefore, flow diversion embolization of a PCOM aneurysm may resolve oculomotor nerve palsies through decreasing arterial pulsations against the nerve or midbrain., (Copyright © 2016. Published by Elsevier Ltd.)

Background/aims: We performed a morphometric analysis of Chiari I malformations to look for predictors of cervical syrinx formation., Methods: Eighteen patients with Chiari I malformation and associated cervical syrinx and 16 patients with Chiari I malformation without associated cervical syrinx were included in the study. Chiari I size was obtained from the radiology report; foramen magnum diameter, cerebellar volume, posterior fossa volume and intracranial volume were calculated using OsiriX software, and average measurements were compared between the two groups., Results and Conclusion: Patients with Chiari I with syrinx had an average tonsillar descent of 13.03 ± 5.31 mm compared to 9.25 ± 3.31 mm in the Chiari I without syrinx group (p < 0.05). Patients with Chiari I and syrinx also showed increased cerebellar crowding with a higher cerebellar volume to posterior fossa volume ratio; however, this difference was not significant (0.83 vs. 0.81; p = 0.1872). No difference between groups was found in posterior fossa volume, intracranial volume and foramen magnum diameter. Therefore, only Chiari I size based on the extent of tonsillar herniation was found to be a determinant of cervical syrinx formation., (© 2016 S. Karger AG, Basel.)

Background: The dura mater can be easily biopsied during most cranial neurosurgical operations. We describe a protocol that allows for robust generation of induced pluripotent stem cells (iPSCs) and neural progenitors from acutely harvested dura mater., Objective: To generate iPSCs and neural progenitor cells from dura mater obtained during ventriculoperitoneal shunt surgery., Methods: Dura was obtained during ventriculoperitoneal shunt surgery for normal pressure hydrocephalus from a 60-year-old patient with severe cognitive impairment. Fibroblasts were isolated from the dural matrix and transduced with nonintegrating Sendai virus for iPSC induction. A subset of successfully generated iPSC clones underwent immunocytochemical analysis, teratoma assay, karyotyping, and targeted neural differentiation., Results: Eleven iPSC clones were obtained from the transduction of an estimated 600,000 dural fibroblasts after 3 passages. Three clones underwent immunocytochemical analysis and were shown to express the transcription factors OCT-4, SOX2, and the embryonic cell markers SSEA-4, TRA-1-60, and Nanog. Two clones were tested for pluripotency and formed teratomas at the injection site in immunodeficient mice. Three clones underwent chromosomal analysis and were found to have a normal metaphase spread and karyotype. One clone underwent targeted neural differentiation and formed neural rosettes as well as TuJ1/SOX1-positive neural progenitor cells., Conclusions: IPSCs and neural progenitor cells can be efficiently derived from the dura of patients who need to undergo cranial neurosurgical operations. IPSCs were obtained with a nonintegrating virus and exhibited a normal karyotype, making them candidates for future autotransplantation after targeted differentiation to treat functional deficits., (Copyright © 2015. Published by Elsevier Inc.)

Obstructive sleep apnoea (OSA) is increasingly recognised as a source of perioperative morbidity and mortality. We describe a patient with severe OSA who developed transient contrast encephalopathy after elective coiling of an anterior communicating artery aneurysm. Contrast extravasation led to cerebral oedema, seizures and delirium, which eventually completely resolved. OSA is known to be associated with a proinflammatory state that leads to hypertension, impaired endothelial repair capacity and endothelial dysfunction. Further studies are needed to clarify whether OSA increases the risk of endovascular procedures., (2015 BMJ Publishing Group Ltd.)

CrossFit is a high-intensity strength and conditioning program that has gained popularity over the past decade. Potential injuries associated with CrossFit training have been suggested in past reports. We report three cases of cervical carotid dissection that are associated with CrossFit workouts. Patient 1 suffered a distal cervical internal carotid artery (ICA) dissection near the skull base and a small infarct in Wernicke's area. He was placed on anticoagulation and on follow-up has near complete recovery. Patient 2 suffered a proximal cervical ICA dissection that led to arterial occlusion and recurrent middle cerebral artery territory infarcts and significant neurological sequelae. Patient 3 had a skull base ICA dissection that led to a partial Horner's syndrome but no cerebral infarct. While direct causality cannot be proven, intense CrossFit workouts may have led to the ICA dissections in these patients.