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Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.
Background: Improvements in sleep-onset, maintenance, and daytime functioning, are all important outcomes for the treatment of insomnia. These improvements are usually assessed by objective or patient-reported (subjective) measures or both. Some sleep-promoting drugs do not report consistently aligned subjective and objective outcomes. Therefore, we examined concordance in change from baseline (CFB) in sleep parameters (objective/subjective measures) and daytime functioning (subjective measures) in the clinical program of lemborexant (LEM), a dual-orexin receptor antagonist. Methods: Study E2006-G000-304 (NCT02783729), a 1-month, placebo (PBO)- and active-controlled (zolpidem; not discussed here) study, and Study E2006-G000-303 (NCT02952820), a 12-month, randomized, PBO-controlled study (first 6-months), evaluated the efficacy/safety of LEM 5mg (LEM5) and LEM 10mg (LEM10) in subjects with insomnia disorder. The primary/secondary endpoints in both studies included multiple objective/subjective sleep parameters and patient-reported measures, which were assessed for concordance. Results: In both studies, statistically significant improvements with LEM5/LEM10 were reported in multiple objective and patient-reported measures versus PBO, showing a concordance of results, with observed improvements continuing through 12 months. LEM was well tolerated; most treatment-emergent adverse events were mild/moderate. Conclusions: When deciding which sleep agent to prescribe, it is important that improvement can be demonstrated in both objective and patient-reported measures. LEM treatment showed concordance among observed measures.
Background: Brain metastases are frequently seen in neurosurgical practice. Standardised criteria are created to better classify these common pathologies in research studies. This study’s goal was to evaluate RANO-BM criteria’s current thresholds in a cohort of patients with brain metastases managed by SRS. Methods: We performed a retrospective metastasis-level analysis of patients treated with SRS for brain metastases. The data collected included cohort demographics, metastases characteristics, outcomes, and the rate of true positives, false negatives, true negatives and false positives as defined by RANO-BM criteria at last follow-up before second SRS. Results: 251 metastases in 50 patients were included in the analysis. RANO-BM criteria using current thresholds yielded a sensitivity of 38%, a specificity of 95%, a positive predictive value of 71% and a negative predictive value of 84%. Modified RANO-BM criteria using absolute diameter differences of 2.5 mm yielded a sensitivity of 83%, a specificity of 87%, a positive predictive value of 67% and a negative predictive value of 94%. Pseudoprogression occurred significantly earlier than tumor progression, with a median time of onset of 6.9 months and 12.1 months respectively. Conclusions: Current RANO-BM criteria unreliably identifies clinically relevant tumor progression, but are useful in assessing diameter increases caused by tumor progression and pseudoprogression.
Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI.
Methods:
We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods.
Results:
The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI.
Conclusion:
DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
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: Malignant gliomas are the most common and deadly brain tumors. Mean survival rate for a patient diagnosed with a glioblastoma multiforme (GBM) remains slightly over one year. Standard of care consists of treatment with temozolomide (TMZ) and radiotherapy. Recent work has highlighted functions of long non-coding RNAs (lncRNAs) in GBM progression and TMZ response even though the information regarding these newly discovered molecules is sparse. The overarching objective of this project was thus to assess the expression of select lncRNAs in GBM tumor samples and in models of TMZ resistance. Methods: A qRT-PCR-based approach was undertaken to measure six lncRNAs in 19 primary GBM samples, four GBM cell lines and in-house developed TMZ-resistant GBM cells. Results: Elevated levels of Hotair and H19 were observed in primary GBM tumors while decreased expression of MEG3 was recorded in the same samples. Interestingly, levels of PANDA increased 3.4-fold in GBM cells resistant to TMZ when compared with their sensitive counterparts. Conclusions: Overall, this work provides evidence of lncRNA deregulation in GBM tumors and reveals a previously unexplored lncRNA potentially involved in TMZ resistance. Modulation of lncRNA targets via RNAi-mediated approaches is envisioned to clarify their function and to strengthen their position as therapeutic options in GBMs.
Phomopsis convolvulus Ormeno, a fungus, reduced growth and regeneration of field bindweed under greenhouse environments. Field bindweed seedlings at the cotyledon stage were severely injured and killed (95% mortality) with 108 conidia/m2. Three- to five-leaf seedlings (2 weeks old) were controlled when inoculated with 109 conidia/m2 (70% mortality; 98 and 89% reduction in dry weight of aboveground biomass and roots, respectively). This inoculum density reduced aboveground and root biomass, and adversely affected regeneration of 4-week-old seedlings and established plants, but few plants were killed. In controlled-environment studies, two inoculations were superior (P = 0.02) to one inoculation in reducing foliage aboveground of well-established seedlings (4 weeks old). However, new shoots produced between the first and second inoculation treatments were less diseased than expected.
Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.
Background: Improving diagnostic and therapeutic tools associated with glioblastoma multiforme (GBM), an aggressive brain tumour, is crucial as average patient survival remains slightly over a year. Challenges include early diagnosis and acquired drug resistance. Improving these challenges notably require a multidisciplinary team and a dedicated brain tumour specimen collection initiative. We hypothesize that implementing such an approach in Moncton would provide significant benefits to GBM patients and researchers in New Brunswick. Methods: A Brain Tumour Tissue Repository was instigated to collect and preserve primary tumour specimens. Storage of circulating samples from patients undergoing temozolomide (TMZ) therapy was also performed. In parallel, molecular leads were investigated in different GBM models to identify therapeutic targets. Results: Collection of 7 primary specimens was accomplished in 2016. Over 15 primary samples are housed in the tumour biorepository to date with circulating samples collected from 3 patients. Additionally, numerous deregulated non-coding RNAs were identified by qRT-PCR in GBM models and shown to be modulated following TMZ treatment warranting further investigation. Conclusions: Overall, these results provide novel therapeutic leads for GBMs and, most importantly, highlight the instigation of a New Brunswick-based brain tumor biorepository which will undoubtedly strengthen brain tumour research in the Maritimes.
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.
Background Currently, the literature lacks reliable data regarding operative case volumes at Canadian neurosurgery residency programs. Our objective was to provide a snapshot of the operative landscape in Canadian neurosurgical training using the trainee-led Canadian Neurosurgery Research Collaborative. Methods: Anonymized administrative operative data were gathered from each neurosurgery residency program from January 1, 2014, to December 31, 2014. Procedures were broadly classified into cranial, spine, peripheral nerve, and miscellaneous procedures. A number of prespecified subspecialty procedures were recorded. We defined the resident case index as the ratio of the total number of operations to the total number of neurosurgery residents in that program. Resident number included both Canadian medical and international medical graduates, and included residents on the neurosurgery service, off-service, or on leave for research or other personal reasons. Results: Overall, there was an average of 1845 operative cases per neurosurgery residency program. The mean numbers of cranial, spine, peripheral nerve, and miscellaneous procedures were 725, 466, 48, and 193, respectively. The nationwide mean resident case indices for cranial, spine, peripheral nerve, and total procedures were 90, 58, 5, and 196, respectively. There was some variation in the resident case indices for specific subspecialty procedures, with some training programs not performing carotid endarterectomy or endoscopic transsphenoidal procedures. Conclusions: This study presents the breadth of neurosurgical training within Canadian neurosurgery residency programs. These results may help inform the implementation of neurosurgery training as the Royal College of Physicians and Surgeons residency training transitions to a competence-by-design curriculum.
The difficulty of monitoring growth parameters of climbing invasive plants subjected to different control options can be overcome by using standardized support structures (trellises). The utility of such support structures on aboveground biomass accumulation and fruit production was demonstrated using the invasive climber, bridal creeper in three invaded nature reserves near Perth in Western Australia. Mean above-ground plant biomass for plots provided with trellises ranged from 204 ± 38 g/m2 to 336 ± 31 g/m2, whereas it ranged from 66 ± 10 g/m2 to 118 ± 10 g/m2 in plots with no trellises. The mean number of fruits/m2 produced on shoots in plots provided with trellises ranged from 424 ± 159 to 3,787 ± 873 and was up to almost four orders of magnitude greater than the number of fruits produced on plants in plots with no trellis (ranging from 0 to 5.25 ± 7.9). The use of standardized trellises also showed that fruit volume and fruit seed number can vary significantly between sites. Standardized trellises have been installed at sites across Australia to assess the long-term impact of biological control agents introduced to manage bridal creeper.
Among the solar proxies, κ1 Cet, stands out as potentially having a mass very close to solar and a young age. We report magnetic field measurements and planetary habitability consequences around this star, a proxy of the young Sun when life arose on Earth. Magnetic strength was determined from spectropolarimetric observations and we reconstruct the large-scale surface magnetic field to derive the magnetic environment, stellar winds, and particle flux permeating the interplanetary medium around κ1 Cet. Our results show a closer magnetosphere and mass-loss rate 50 times larger than the current solar wind mass-loss rate when Life arose on Earth, resulting in a larger interaction via space weather disturbances between the stellar wind and a hypothetical young-Earth analogue, potentially affecting the habitability. Interaction of the wind from the young Sun with the planetary ancient magnetic field may have affected the young Earth and its life conditions.
A method is proposed by which a direct numerical simulation of the compressible Navier-Stokes equations may be embedded within a more general aeronautical CFD code. The method may be applied to any code which solves the Euler equations or the Favre-averaged Navier-Stokes equations. A formal decomposition of the flowfield is used to derive modified equations for use with direct numerical simulation solvers. Some preliminary applications for model flows with transitional separation bubbles are given.
Background: Because glioblastoma is currently incurable, the goal of therapy is the optimization of the patient’s quality of life (QOL). Tumor location is critical in screening surgical candidates, yet the impact of tumor location on QOL has never been demonstrated. By using a novel computer-driven algorithm, we set out to investigate the impact of tumor location on QOL. Methods: The tumors of fourty consecutive glioblastoma patients were segmented and the Euclidian distance between 90 brain regions and each tumor’s margin was calculated and correlated to the patients’ self-reported QOL as measured by the SNAS questionnaire. Results: QOL was statistically associated with proximity to three areas: the right para-hypocampal gyrus, the right posterior cingulate cortex and the right postcentral gyrus. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in large-scale networks involved in high-order functions such as visuospatial memory. While harder to detect with a bedside clinical examination, such deficits are likely more impactful on QOL than those related to the motor cortex or Broca’s area. Conclusions: Tumor proximity to right parietooccipital region are associated with decreased QOL. This should be considered in the management strategies of glioma patients.
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.