BACKGROUND: The genetic determinants and mechanisms underlying intracranial aneurysm rupture (rIA) are largely unknown. Given the ∼50% mortality rate of rIA, approaches to identify patients at high risk will inform screening, diagnostic, and preventative measures. OBJECTIVE: To identify and characterize the genetic basis of rIA. METHODS: We perform a genome-wide association study (GWAS) using functional genomics approaches to identify and characterize rIA-associated loci and genes. We perform a meta-analysis across 24 published GWAS of rIA. Single nucleotide polymorphisms, gene-burden analysis, and functional genomics identify and characterize genetic risk factors for rIA. RESULTS: Our cohort contains 84 353 individuals (7843 rIA cases and 76 510 controls). We identify 5 independent genetic loci reaching genome-wide significance (P < 5.0 × 10−8) for rIA including rs12310399 (FGD6, odds ratio = 1.16), which has been implicated in prior GWAS of IA. We then quantified gene-level mutation burden across ∼20 000 genes, and only FGD6 (containing 21 rIA-associated single nucleotide polymorphisms) reached transcriptome-wide significance. Expression quantitative trait loci mapping indicates that rs12310399 causes decreased FGD6 gene expression in arterial tissue. Next, we used publicly available single-cell RNA sequencing of normal human cerebrovascular cells obtained during resection surgery and identify high expression of FGD6 in 1 of 3 arterial lineages but absent in perivascular cells. These data suggest how alterations in FGD6 may confer risk to rIA. CONCLUSION: We identify and characterize a known risk loci for IA, but not for rIA, containing FGD6. Elucidation of high-risk genetic loci may instruct population-genetic screening and clinical-genetic testing strategies to identify patients predisposed to rIA.

BACKGROUND: The tenets of minimally invasive neurosurgery require small craniotomies that nevertheless afford sufficient surgical freedom to safely accomplish the operative goal. OBJECTIVE: To present a novel technique which couples surgical rehearsal in virtual reality (VR) with navigation-integrated, microscope-synchronized augmented reality (AR) to optimize minimally invasive openings. METHODS: A retrospective review of the senior author's early experience with this mixed reality (VR + AR) platform was conducted. Patient-specific VR models were rendered from standard computed tomography/MRI. Surgical rehearsal with these models created templates with the optimal opening, which were integrated with the AR system. In surgery, the templates were projected through a navigation-tracked microscope and appeared as AR objects onto the patient. The templates guided the planning of the incision and steps of the approach. RESULTS: Sixteen patients were included in this study, 11 women and 5 men (33-79 years; median: 59.5). Twelve operations were performed for mass lesions and 4 for microvascular decompression for trigeminal neuralgia. There were no intraoperative adverse events related to AR. For 15 patients (94%), the templates provided major advantage in optimizing the bony opening and guided the operation to the specific anatomic location chosen preoperatively. For 1 patient, the AR template guided the drilling away from the critical structures inside the temporal bone. In addition, 3-dimensional AR markers relieve the surgeon from ergonomically cumbersome monitor-based navigation (Video 1). CONCLUSION: This novel mixed reality platform combines surgical rehearsal in VR and navigation-integrated, microscope-synchronized overlay of AR templates to ensure that optimal exposure is efficiently obtained.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) has become one of the mainstays of treatment for patients with metastatic brain tumors. However, metastatic tumors with a large cystic component often exceed the size limit for safe and effective SRS. In such cases, surgical resection may not be the preferred first method of treatment, due to tumor location, patient co-morbidities, and patient preference. In these patients, volume reduction by cyst aspiration (CA) followed by SRS may be a viable alternative treatment option. OBJECTIVE To present the treatment of patients with cystic metastases using reservoir placement followed by SRS. METHODS Nine patients were treated with this method. We performed reservoir insertion for the aspiration of cystic component in each patient and followed that with outpatient SRS. RESULTS Mean overall volume reduction from this treatment method was 78.5%. Mean volume reduction from the CA alone was 59.8%, and after SRS, a further 66.6%, accounting for some cyst reaccumulation between the time of surgery and SRS. Repeat reservoir aspiration was done a total of 10 times in 5 patients. Our study showed local tumor control in 7 of 9 patients (77.8%), while 2 patients required later surgical resection of their tumors. CONCLUSION CA with reservoir placement followed by SRS is a good option for patients with large cystic brain metastases. The reservoir allows for repeat aspiration if needed. Catheter placement at the center of the cyst, and SRS within 2 to 3 wk of surgery, can maximize the likelihood of a successful outcome.

ABSTRACT Prior work has shown that the human placenta is an available and realistic model for microdissection simulation. We sought to find a measurable improvement in the technical skills of neurosurgical residents with deliberate practice of microdissection tasks using a placental model. Postgraduate year (PGY) 1 to 3 neurosurgery residents were consented. A 1-min video of each participant's baseline skills skeletonizing placental vessels was recorded. Participants underwent 10 practice sessions with intermittent informal feedback for 30-60 min over 18 mo. Another 1-min video was recorded following the 10th dissection. The videos were blinded and assessed by 3 board eligible or certified microsurgical neurosurgeons using a modified Objective Structured Assessment of Aneurysm Clipping Skills. Performance was compared via t-testing among four domains: instrument handling, time flow and forward planning, quality of dissection, and respect for tissue. Microdissection, instrument handling, and quality of dissection were significantly improved after deliberate practice with the placental simulator (P < .05). Improvement was seen in time flow and forward planning and respect for tissue; however, this failed to be significant. Subjectively, residents expressed enjoyment performing the exercise. They also expressed a desire for demonstrations or videos to watch before practice sessions. The placental simulation model provides microsurgical skill development with minimal deliberate practice sessions. Practice exercises are favorably regarded and interest in continuing them is strong by residents. Residents expressed a desire to make the dissection more deliberate with demonstration, breakdown of steps, and mimicry, which could improve the effectiveness and enjoyment of the skills session.

ABSTRACT BACKGROUND Cranioplasty is a procedure commonly performed as the next step in management for patients with decompressive craniectomy. It is commonly associated with complications that might result in implant failure and reoperation. Tissue engineering and regenerative medicine (TERM) involve the development of biological substitutes that restore tissue function and regrow and replace damaged tissues. TERM is a potential solution that might allow for improved long-term outcomes in cranioplasty. OBJECTIVE To present a case series that describes the management and treatment outcomes of using TERM in cranioplasty, using polycaprolactone-tricalcium phosphate (PCL-TCP) implants in 2 patients. METHODS In 2 young adults, large bone defects of the skull following decompressive craniectomy were reconstructed using patient-specific implants manufactured from PCL-TCP. Bone marrow aspirate was used as autologous biologic that incorporates stem cell and growth factors into the implant. RESULTS Both patients recovered without any complications following surgery. Physical examination shows favorable healing outcomes with the defect area having a hard texture upon palpation. Postoperative imaging performed at 8 and 20 months for each patient, respectively, demonstrated ossification over the defect area. CONCLUSION Satisfactory bone growth is seen with TERM cranioplasty. The PCL-TCP implant is a novel and recommendable alternative to currently available patient-specific implants used in cranioplasty. TERM cranioplasty is the potential solution to the quest of finding the ideal cranioplasty implant.

While many researchers have documented the presence of racism in education, the literature also suggests that the existence of racism tends to be denied and that, further, teachers are not well equipped to deal with the more covert expressions of racism. As teacher educators this is a concern that has led us to reconceptualize our curriculum. If future teachers are to engage their own students in anti-racism in a meaningful and constructive way to address the everyday racism that many of us take for granted, then they themselves must actively explore how their own racial identities have been shaped within a broader racist culture. When we say that we want to 'engage' students, what we want to do is to create a climate that allows them to move beyond intellectualising 'the problem' to actually connecting with racism in all its manifestations on a physical/emotional level. Thus, the aim of this paper is to tell the story of a group of twenty-three Australian teacher education students as they engaged in exploring the workings of prejudice and discrimination within the context of a simulation game designed to expose white privilege and to challenge racism at both the individual as well as the institutional level.