Background: Delayed Cerebral Ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. A paucity of high-quality evidence is available to guide the management of DCI. As such, our objective was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI. Methods: The Canadian Neurosurgery Research Collaborative (CNRC) performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. The survey was distributed to members of the Canadian Neurosurgical and Neurocritical Care Societies, respectively. Responses were analyzed using quantitative and qualitative methods. Results: The response rate was 129/340 (38%). Agreement among respondents included the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for prevention of DCI. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients felt to require intravenous milrinone, intra-arterial vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI. Conclusions: DCI is an important clinical entity for which no consensus exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the diagnosis and management of DCI.

Background: Extracranial traumatic vertebral artery injury (eTVAI) is common following non-penetrating head and neck trauma. Most cases are initially asymptomatic with an increased risk for stroke. Consensus is lacking regarding screening, treatment, and follow-up of asymptomatic patients with eTVAI. Our objective was to investigate national practice patterns reflecting these domains. Methods: An electronic survey was distributed via the Canadian Neurological Sciences Federation and Canadian Spine Society. Two case-based scenarios featured asymptomatic patients with eTVAI. Case 1: non-displaced cervical lateral mass fracture; angiography stratified by luminal diameter reduction. Case 2: complex C2 fracture; angiography featuring pseudoaneurysm dissection. Analysis: descriptive statistics. Results: Response Rate: 108 of 182 participants (59%), representing 20 academic institutions.

Case 1: 78% of respondents would screen using CTA (97%), immediately (88%). Most respondents (97%) would initiate treatment, using aspirin (89%) for 3-6 months (46%).

Case 2: 73% of respondents would screen using CTA (96%), immediately (88%). The majority of respondents (94%) would initiate treatment, using aspirin (50%) for 3-6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy.

In both cases, the majority of respondents would follow-up clinically or radiographically every 1-3 months, respectively. Conclusions: This study highlights consensus in Canadian practice patterns for the workup and management of asymptomatic eTVAI.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

Introduction: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Background: Insertion of an external ventricular drain (EVD) is performed to treat elevated intracranial pressure. EVD catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH) and suboptimal catheter placement. As part of the Canadian Neurosurgery Research Collaborative, we sought to investigate the national rate of such complications and their risk factors. Methods: Prospective study of 273 patients from eight academic Canadian neurosurgery centres Results: Infection rate was 6% and predicted by smaller incisions and not peri-procedure antibiotics, tunneling distance, type of antiseptic used or catheter flushing (p>0.05). The mean duration of EVD was 17.7±3.7 in ECI and ventriculitis group which was significantly higher than in patients without ECI (9.4±8.1) (p=0.045). Although the risk of developing ICH was 9.3%, symptomatic ICH was rare. Pre-procedure pharmacological DVT prophylaxis predicted EVD-related ICH(OR 4.73). The rate of suboptimal catheter location was 31% and predicted by the number of passes (p=0.02), but not image guidance, level of training or catheter placement in an operating room setting (p>0.05). Conclusions: This study reports EVD complication rates and their associated risk factors observed within an academic, multicentre Canadian cohort. This information will help to identify strategies to increase the safety of this common neurosurgical procedure.

Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them

Background: No standardized method of resident operative-case logging exists. Our study sought to develop a standardized form used by residents to log operative-cases. Methods: Members of the Canadian Neurosurgery Research Collaborative (CNRC), a national resident-led research organization have created a standardized document based on the current Royal College objectives for operative procedures (section 5). Modifications to structure and content will be guided via consensus from Canadian neurosurgery program-directors. Results: Program directors in each CNRC collaborative institution will be asked to modify the standardized form. The CNRC currently involves thirteen of the fourteen Canadian neurosurgery residency programs. Additional consensus, if necessary, can be reached at the Royal College meeting for program directors of neurosurgery March 20th 2017. Conclusions: A standardized operative-case log represents the first step in a prospective study towards compiling operative volume of all Canadian neurosurgical residents over one academic year. Such data will be essential to guide informed decisions with regard to Royal College requirements as Canadian neurosurgical programs transition to a competency based framework.

Background: Communicating with senior neurosurgical colleagues during residency necessitates a reliable and versatile smartphone. Smartphones and their apps are commonplace. They enhance communication with colleagues, provide the ability to access patient information and results, and allow access to medical reference applications. Patient data safety and compliance with the Personal Health Information Protection Act (PHIPA, 2004) in Canada remain a public concern that can significantly impact the way in which mobile smartphones are utilized by resident physicians Methods: Through the Canadian Neurosurgery Research Collaborative (CNRC), an online survey characterizing smartphone ownership and utilization of apps among Canadian neurosurgery residents and fellows was completed in April 2016. Results: Our study had a 47% response rate (80 surveys completed out of 171 eligible residents and fellows). Smartphone ownership was almost universal with a high rate of app utilization for learning and facilitating the care of patients. Utilization of smartphones to communicate and transfer urgent imaging with senior colleagues was common. Conclusions: Smartphone and app utilization is an essential part of neurosurgery resident workflow. In this study we characterize the smartphone and app usage within a specialized cohort of residents and suggest potential solutions to facilitate greater PHIPA adherence

Background: The Canadian Neurosurgery Research Collaborative (CNRC) was founded in November 2015 as a resident-led national network for multicentre research. We present an annual report of our activities. Methods: CNRC meetings and publications were reviewed and summarized. The status of ongoing and future studies was collected from project leaders. Results: In its first year, the CNRC produced two papers accepted for publication in the Canadian Journal of Neurological Sciences: A CNRC launch letter and a study of operative volume at Canadian neurosurgery residency programs. Three manuscripts are in preparation: 1) a study of the demographics of Canadian neurosurgery residents, 2) an assessment of mobile devices usage patterns and 3) a validation study of the most utilized neurosurgery mobile apps. In addition, protocols for two multi-centre studies are currently undergoing national Research Ethics Board review: A retrospective study of the incidence and predictors of cerebellar mutism and a prospective registry of external ventricular drain procedures and complications. The network is now a registered not-for-profit organization endorsed by the Canadian Neurosurgical Society. Conclusions: The CNRC is a feasibile, relevant and productive resident-led national research network. As the CNRC matures, we look forward to expanding the scope and impact of its projects.

Brain tumours represent the leading cause of childhood cancer mortality, of which medulloblastoma (MB) is the most frequent malignant pediatric brain tumour. Current molecular Nsubgroups of MB recognize distinct disease entities of which activated Wnt signaling (monosomy 6, exon 3 mutations in CTNNB1, and Wnt gene signature) is associated with a distinct subgroup and the best overall outcome. In contrast, only non-Wnt MBs are characterized by metastatic disease, increased rate of recurrence, and poor overall survivorship. Given the excellent clinical outcome in patients with Wnt-driven MB, we aimed to convert treatment-resistant MB subgroups into an ostensibly benign tumour through selective targeting by small molecule Wnt agonists (Wnt3A), GSK3 inhibitors (CHIR99021), and transgenic lines containing a stabilized beta-catenin mutant. Activated Wnt signaling resulted in decreased in vitro self-renewal and promoted differentiation within primary human MB stem cells. The clinical relevance of these findings were demonstrated with an in vivo survival advantage in mice containing orthotopic injections of cells containing a stabilized beta-catenin mutant representative of constitutively active Wnt signaling. Xenografts generated from Wnt-activated tumours were much smaller in size, maintained a much lower rate of proliferation, and reduction in key MB stem cell self-renewal genes (Bmi1, Sox2, Msi1, FoxG1). Our work establishes activated Wnt signaling as a novel treatment paradigm in childhood MB, while providing evidence for the context-specific tumour suppressive function of the canonical Wnt pathway.

Background: The Canadian Neurosurgery Research Collaborative (CNRC) is a new consortium of neurosurgery residency programs set-up to facilitate the planning and implementation of multi-center studies. As a trainee-led organization, it will focus on resident-initiated, resident-driven projects. The goal of this study is to assess the demographics of Canadian neurosurgery residents, with particular focus on their academic and subspecialty interests. Methods: After approval by the CNRC, an online survey will be sent to all Canadian neurosurgery residents and fellows with reminders at 2, 4 and 6 weeks. Anonymous, basic demographic data will be collected. Specific interest towards the various subspecialties, research and academic vs community practice will be measured. The data will be crossed with the ongoing Canadian Neurosurgery Operative Landscape study to assess the impact of case volume on academic and subspecialty interests. Results: This is the first study providing a snapshot of Canadian neurosurgery residents at all levels of training. The study is ongoing and the official results will be presented at the meeting. As one of the first CNRC studies, it will also demonstrate the effectiveness of the collaborative. Conclusions: Understanding the demographics and interests of Canadian neurosurgery residents will allow the CNRC to better fulfill its mission.

Background: The Canadian Neurosurgery Research Collaborative (CNRC) is a trainee-led multi-centre collaboration made up of representatives from 12 of 14 neurosurgical centres with residency programs. To demonstrate the potential of this collaborative network, we gathered administrative operative data from each centre in order to provide a snapshot of the operative landscape in Canadian neurosurgery. Methods: Residents from each training program provided adult neurosurgical operative data for the 2014 calendar year, including the number of surgeries in the subcategories cranial, spinal, and peripheral nerve. Because some residency programs have surgeries distributed among more than one hospital, we calculated mean case load per residency program and per hospital. Results: Interim results from 6 neurosurgery residency programs are presented (with data from other programs forthcoming). Overall, there were on average 2,352 operative cases per residency program (n=6) and 1,176 operative cases per adult hospital (n=12). Among 5 programs with more detailed operative data, the mean numbers of cranial, spinal, peripheral nerve, and miscellaneous surgeries per residency program were 757 (47%), 487 (30%), 47 (3%), and 319 (20%) respectively. Conclusions: We show as a proof-of-concept that a trainee-led nation-wide research collaborative can generate meaningful data in a Canadian context.

Background: The goals of evidence-based neurosurgery are to improve surgical outcomes, reduce complications, and provide an objective basis for altering practice. The need for higher quality studies, typically prospective and multicentre, has been growing especially in light of the evolving complexity of neurosurgical interventions and heterogeneity of patient populations. In the United Kingdom (UK), trainee-led research collaboratives have been established to tackle this problem. Therefore, we sought to evaluate the potential role for a resident-led research collaborative in neurosurgery in Canada based on the UK experience. Methods: A literature review of trainee-led collaboratives was conducted utilizing PubMed and Medline. Identified articles were reviewed for study quality and clinical relevance to explore the potential benefits of collaboratives. Results: In the UK, 27 collaboratives have been established in various specialties by trainees. Some published high quality trials with implications on their clinical fields. Evidence suggests that such endeavors improves trainees’ research skills and may help cultivate a research culture tailored towards clinical trials. Conclusions: Given the growing evidence for research collaboratives in the UK, we propose launching the Canadian Neurosurgery Research Collaborative (CNRC) which currently represents 12 out of 14 neurosurgery programs in Canada, and planning its first multicenter prospective study.