Background: Stroke is often preceded by transient symptoms. Although global stroke rates have been shown to be declining, previous studies have reported inconsistent temporal trends of transient ischemic attacks (TIA). The objective of the current study is to report the temporal trends of TIA admissions and outcomes in Canada over the last 11 years. Methods: We conducted a complete population cohort study using a national administrative database to study the temporal trend of age- and sex-adjusted TIA admission rates in Canada from 2003 to 2013. We also determined the rates of TIA and stroke diagnoses in the emergency department in the province of Ontario during the same period. We used multivariable analyses to study discharge location after acute hospitalization as well as 90-day stroke and/or TIA readmission rates. Results: Of 425,799 admissions to an acute care hospital for all stroke and TIA, 71,443 (16.8%) were TIA. The age- and sex-standardized rates of TIA admission decreased significantly during the study period from 30.0 to 20.6 per 100,000 (p<0.0001). In Ontario, decreasing TIA admissions is mirrored by decreasing rates of TIA directly discharged from the emergency department (55.1 to 46.8 per 100,000, p = 0.002). The odds of 90-day readmission rates for stroke or TIA are also decreasing (adjusted odds ratio, 0.97; 95% confidence interval, 0.96-0.99). Conclusions: We show that TIA admission rates have declined in the past 11 years in Canada, reflecting improved vascular risk reduction and stroke care. Future studies to confirm our findings on improved stroke or TIA recurrence rates are necessary.

Background: Despite the critical role played by neurosurgeons in performing radiosurgery, neurosurgery residents in Canada have limited exposure to radiosurgery during their training. A survey of neurosurgery residents and faculty along with radiation oncology faculty was conducted to analyze perspectives regarding incorporating formal radiosurgery training into the neurosurgery residency curriculum Methods: An online survey platform was employed. Descriptive statistics were used to summarize center and respondent characteristics. Categorical variables were compared using odds ratios and corresponding 95% confidence intervals. The chi-squared test was utilized to assess statistical significance. A value of p<0.05 was considered significant Results: The response rate was 31% (119/381); 87% (102/119) of respondents were from the neurosurgical specialty and 13% (17/119) from radiation oncology. Some 46% of residents (18/40) were “very uncomfortable” with radiosurgery techniques, and 57% of faculty (42/73) believed that dedicated radiosurgery training would be beneficial though impractical. No respondents felt that “no training” would be beneficial. A total of 46% of residents (19/41) felt that this training would be beneficial and that time should be taken away from other rotations, if needed, while 58% of faculty (42/73) and 75% (28/41) of residents believed that either 1 or 1-3 months of time dedicated to training in radiosurgery would suffice Conclusions: Canadian neurosurgeons are actively involved in radiosurgery. Despite residents anticipating a greater role for radiosurgery in their future, they are uncomfortable with the practice. With the indications for radiosurgery expanding, this training gap can have serious adverse consequences for patients. Considerations regarding the incorporation and optimal duration of dedicated radiosurgery training into the Canadian neurosurgery residency curriculum are necessary.

Objective: To determine the referral rate to radiation oncologist (RO), use of postoperative radiotherapy (PORT) and the impact of a clinical practice guideline (CPG) on patients with atypical meningioma (AM). Methods: A retrospective review of meningioma patients (n=526) treated between 2003 and 2013 was undertaken. Patients’ characteristics, extent of surgical resection (EOR), RO referral, PORT, date and treatment of first recurrence were collected for all patients >18 years with a new diagnosis of AM after surgical resection (n=83). Progression free survival (PFS) and overall survival (OS) according to EOR were assessed by the Log-Rank test of Kaplan-Meier survival. Results: Median age was 57 years. EOR was gross total (GTR) in 44 patients, subtotal (STR) in 36 patients and 3 patients had unknown EOR. RO referral rate was 26.5% (n=22); 5 patients initially had GTR and 17 had STR. Only 7 patients received PORT. At a median follow up time of 29 months, recurrences occurred in 28 patients, 4 had GTR, 21 had STR and 3 had an unknown EOR. With PORT, 2 patients developed recurrence. 5-year PFS was 62% after GTR and 33% after STR (P=0.002). 5-year OS was 92% after GTR and 83% after STR (P=0.45). Conclusion: In this cohort with AM, RO referral rate was low and was not influenced by the CPG. Use of PORT was also low. Given the lack of conclusive evidence supporting PORT in such patients, a multidisciplinary approach, including RO consultation, is needed to provide patients with optimal and individualised care.

Background: Optic pathway gliomas (OPG) represent 5% of pediatric brain tumours. Visual acuity measures are used to evaluate treatment response. Current clinical tests to assess visual field integrity are subjective and require verbal cooperation. Thus, the objective of this study was to evaluate the clinical effectiveness of Steady State Visual Evoked Potentials (ssVEPs) to measure visual field integrity in a non-invasive and objective manner. Methods: SsVEPs were obtained in ten children with OPGs and 42 controls ages 3 to 21. The stimuli consisted of two circular dartboard patterns stimulating fovea and peripheral zones at two flickering frequencies, so that central and peripheral visual fields could be assessed simultaneously. The test consisted of eight stimuli presentations of 10 seconds. Results: Results indicate significantly lower ssVEP amplitudes in children with OPGs (M=2.52, 95% CI [1.13, 3.92]) compared to controls (M=13.26, 95% CI [8.85, 17.67]) in the central visual field (p=.021). However, no between group differences were detected in the peripheral field (p >.05). There were no significant differences between age groups (p>0.05). Conclusions: This objective, affordable, and non-invasive method appears to be effective in detecting central visual field deficits in children with OPGs rapidly and consistently.

Background: Cross-clamp ischemia during carotid endarterectomy can be prevented with carotid bypass shunts in vulnerable patients identified by cerebral monitoring for ischemia. We compared transcranial cerebral oximetry (TCO) with carotid stump pressure measurements for selective shunt use. Methods: We prospectively collected data on 300 consecutive patients operated on under general anesthesia between 2009 and 2016. Shunts were inserted for a 10% or greater drop in cerebral saturations and/or a mean stump pressure less than 40 mmHg. Results: Seventy-five patients, 25% of the study population, were shunted. The indication was a combined desaturation and stump pressure in 38 (50% of the shunted group), desaturation alone in 11 patients (15%), and a low stump pressure alone in 26 patients (35%). There were no significant differences in baseline characteristics between those patients who were or were not shunted, except angiographic collateral blood supply, which was more commonly identified in patients who were not shunted. A watershed infarct occurred in just one patient with borderline TCO and stump pressure measurements in whom a shunt was not used. Conclusions: There was poor concordance between TCO and stump pressures, but using both in determining the need for shunt use almost eliminated cross-clamp ischemia in this series of 300 carotid endarterectomy patients.

Background: Hospitalization data underestimate the occurrence of transient ischemic attack (TIA). As TIA is frequently diagnosed in primary care, methodologies for the accurate ascertainment of a TIA from physician claims data are required for surveillance and health systems planning in this population. The present study evaluated the diagnostic accuracy of multiple algorithms for TIA from a longitudinal population-based physician billing database. Methods: Population-based administrative data from the province of British Columbia were used to identify the base population (1992–2007; N=102,492). Using discharge records for hospital admissions for acute ischemic stroke with a recent (<90 days) TIA as the reference standard, we performed receiver-operating characteristic analyses to calculate sensitivity, specificity, positive and negative predictive values and overall accuracy, and to compare area under the curve for each physician billing algorithm. To evaluate the impact of different case definitions on population-based TIA burden, we also estimated the annual TIA occurrence associated with each algorithm. Results: Physician billing algorithms showed low to moderate sensitivity, with the algorithm for two consecutive physician visits within 90 days showing the highest sensitivity at 37.7% (CI95%=37.4–38.1). All algorithms demonstrated high specificity and moderate to high overall accuracy, resulting in low positive predictive values (≤5%), low discriminability (0.53–0.57) and high false positive rates (1 – specificity). Population-based estimates of TIA occurrence were comparable to prior studies and declined over time. Conclusions: Physician billing data have insufficient sensitivity to identify TIAs but may be used in combination with hospital discharge data to improve the accuracy of estimating the population-based occurrence of TIAs.

Background: Radiotherapy with procarbazine, lomustine, and vincristine improves overall survival (OS) in patients with 1p19q co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma. Methods: This retrospective analysis investigated outcomes in patients with 1p19q co-deleted/partially deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and prognostic factors using the Cox proportional hazard model. Results: A total of 106 patients (between December 1997 and December 2013) were included. Median age was 40 years (19-66), 58 were male (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27 (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients, respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85 patients with sufficient material. Upfront treatment was given in 72 (68%) patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47 patients (44%) was 34.7 months and 41.2 months in 9 patients with co-deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma who received upfront temozolomide alone. Median OS was not reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On multivariable analysis for all patients, receipt of therapy upfront versus none (p=0.04), PS 1 versus 0 (p<0.001) and 1p19q co-deletion/incomplete deletion versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate dehydrogenase-1 status was not prognostic for PFS. Conclusions: With similar survival patterns in low-grade/anaplastic gliomas, molecular characteristics may be more important than histological grade. Longer follow-up and results of prospective trials are needed for definitive guidance on treatment of these patients.

Background: The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. We aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Methods: Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with patients not acquiring CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: A total of 22 patients were included. Medulloblastoma was the most common pathology among CM patients (91%). Tumor attachment to the floor of the fourth ventricle (OR, 6; 95% CI, 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR, 5; 95% CI, 0.5-236.5) were found to have the highest association with CM. Conclusions: Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia are relatively more prevalent in patients with CM. Collectively, our work calls for a larger multi-institutional study of CM patients to further investigate the determinants and management of CM to potentially minimize its development and predict onset.

Objective: Given the difficult to navigate literature on social determinants in Indigenous traumatic brain injury (TBI) we wished to identify all available literature on the social determinants of health linked to TBI in the North American Indigenous populations. Methods: We performed a systematically conducted review. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to January 2016. A two-step review process of the search results was performed, applying defined inclusion/exclusion criteria. The final group of articles had the data extracted and summarized. Results: Ten manuscripts were identified to discuss some social determinant linked to TBI in the North American Indigenous populations. Two studies were focused on Canadian populations, with the remaining 8 studies focused on populations within the United States. Six social health determinants were identified within the studies, including: Rural location (Physical Environment) in seven studies, Male gender in five studies and Female gender in one study (in the setting of interpersonal violence) (Gender), Substance use in four studies and failure to utilize personal protective equipment in one study (Personal Health Practices and Coping Skills), Interpersonal Violence in one study (Social Environment), availability of rehabilitation services in one study (Health Services), and lack of family and friend presence during meetings with healthcare professionals in one study (Social Support Network). Conclusions: To date, little literature is available on the social determinants that impact TBI in the North American Indigenous population. Further research is warranted to better determine the incidence and social determinants associated.

Renaut corpuscles are cylindrical hyaline structures that arise from the peripheral nerve perineurium and project into the endoneurium. Despite their earlier accurate description in the French and German literature, Kernohan and Woltman (1938) reported very similar structures as “nerve infarcts” in a case series of vasculitic neuropathy. Krücke (1955) deserves credit for discovering this error and further explaining how peripheral nerves react differently (from brain parenchyma) to ischemia. We tried to elucidate the reason why Kernohan and Woltman, and others, made this scientific error by describing the historical evolution of our understanding of the structure and function of Renaut corpuscles.

Background: Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. Methods: The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. Results: Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. Conclusions: We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.

Background: Our study evaluated the perioperative quality of life (QoL) in Cushing’s disease (CD) patients, along with correlations between patient variables and cure rate. Methods: The 36-item Short-Form Health Survey (SF)-36 questionnaire was used to assess perioperative QoL. Patients completed one survey preoperatively and two surveys postoperatively. Retrospective chart review was conducted to collect SF-36 data as well as examine variables including: age, hospital stay, size of tumour, pathological diagnosis, timing of cure, and complication rates. Statistical analysis was conducted on the scores reported by the SF-36, and were compared with the normal Canadian population values, and to a sample of QoL from nonfunctioning pituitary tumour patients. This project was approved by University of British Columbia Research Ethics Board #H15-01572. Results: In general, CD patients have relatively poor QoL that does improve as expected when cured, but not quite to normal levels. Factors associated with cure included presence of macroadenoma, confirmatory pathology, and patient age. Postoperative timing of cure appears to affect the durability of cure, with an immediate cure having a higher durability rate than delayed cure. Most recurrences occurred within 10 months postoperatively. Conclusions: This review of the perioperative QoL in CD helps to illustrate how QoL changes throughout the treatment process, how QoL compares to normal Canadian population levels, and how QoL compares to patients with nonfunctioning pituitary adenomas. As treatment outcome has such a high impact on QoL, the variables identified in this study will help to better inform patients about the treatment course.

Background: Subthalamic nucleus deep brain stimulation (STN–DBS) has become a standard treatment for many patients with Parkinson’s disease (PD). The reported clinical outcome measures for procedures done under general anesthesia (GA) compared to traditional local anesthetic (LA) technique are quite heterogeneous and difficult to compare. The aim of this systematic review and metaanalysis was to determine whether the clinical outcome after STN–DBS insertion under GA is comparable to that under LA in patients with Parkinson’s disease. Methods: The databases of Medline Embase, Cochrane library and Pubmed were searched for eligible studies (human trials, English language, published between 1946 and January of 2016). The primary outcome of this study was to assess the postoperative improvement in the symptoms, evaluated using either Unified Parkinson’s Disease Rating Scale (UPDRS) scores or levodopa equivalent dosage (LEDD) requirement. Results: The literature searches yielded 395 citations and six retrospective cohort studies with a sample size of 455 (194 in GA and 261 in LA) were included in the analysis. Regarding the clinical outcomes, there were no significant differences in the postoperative Unified Parkinson’s disease rating scale and levodopa equivalent drug dosage between the GA and the LA groups. Similarly, the adverse events and target accuracy were also comparable between the groups. Conclusions: This systematic review and meta-analysis shows that currently there is no good quality data to suggest equivalence of GA to LA during STN-DBS insertion in patients with PD, with some factors trending towards LA. There is a need for a prospective randomized control trial to validate our results.

Background: Critical illness polyneuropathy (CIN) and critical illness myopathy (CIM), together “ICU-Acquired weakness (ICUAW),” occur frequently in septic patients. One of the proposed mechanisms for ICUAW includes prolonged inactivation of sodium channels. Propofol, used commonly in patients with acute respiratory failure (ARF), primarily acts via enhancement of GABAergic transmission but may also increase sodium channel inactivation, suggesting a potential interaction. Methods: Electronic medical records and EMG reports of patients with ICUAW and a diagnosis of either sepsis, septicaemia, severe sepsis, or septic shock, concurrent with a diagnosis of acute respiratory failure (ARF), were retrospectively analyzed in a single center university hospital. Results: 74 cases were identified (50.0% men, age 58±14 years), and compared to age- and sex-matched controls. Of these, 51 (69%) had CIN, 19 (26%) had CIM, and 4 (5%) had both. Propofol exposure was significantly higher in patients with ICUAW compared to controls (63.5% vs. 33.8%, p<0.001). The odds ratio of developing ICUAW with propofol exposure was 3.4 (95% CI:1.7-6.7, p<0.001). Patients with ICUAW had significantly more days in hospital (59±44 vs. 30±23) and ICU (38±26 vs. 17±13), days dependent on mechanical ventilation (27±21 vs. 13±16), and rates of tracheostomy (79.7% vs. 36.5%) and gastrostomy (75.7% vs. 25.7%) (all p<0.001). They also received a significantly higher number of distinct intravenous antibiotics, cumulative days of antibiotic therapy, and exposure to vasopressors and paralytics. Conclusions: Propofol exposure may increase the risk of ICUAW in septic patients. An interaction through sodium channel inactivation is hypothesized.

Background: Although D-dimer levels are significantly associated with cardioembolic infarction, the significance of D-dimer levels in relation to the severity and functional outcomes of other stroke subtypes, such as lacunar and large artery atherosclerosis infarction, remains unclear. The purpose of this study was to evaluate whether elevated initial D-dimer levels are significantly and cross-sectionally associated with poor functional outcomes at each time point during a 9-month follow-up period. We also investigated the significance of D-dimer levels in longitudinal temporal changes of functional outcomes in these patients. Methods: We recruited 146 patients with lacunar infarction and 161 patients with large artery atherosclerosis infarction who were consecutively admitted to our hospital after acute stroke. Serum D-dimer levels were evaluated initially and the modified Rankin scale were measured initially and at 1-, 3-, 6-, and 9-month follow-up visits. Results: Patients with higher D-dimer levels had significantly worse initial functional outcomes, and these worse outcomes were maintained throughout the 9-month follow-up period compared with the low D-dimer group. However, regardless of stroke subtype, D-dimer levels did not influence long-term changes in functional outcomes over the 9-month follow-up period. Conclusion: This study suggests that elevated D-dimer levels can be used as a surrogate marker for poor functional outcomes only during the acute stage. Further evaluation of serum D-dimer levels could provide a helpful predictive marker for stroke prognosis.

Background: Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in Capicua (CIC), located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. Methods: Transcriptome profiling of CIC knockout HEK293 cell lines generated using CRISPR was performed using microarray. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence. Transcript and protein changes of CIC targets were tested using RT-qPCR and Western blot following ATXN1L siRNA knockdown. Results: Transcriptomic profiling of CIC knockout cell lines resulted in a list of candidate CIC target genes validated against clinical samples. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction. Derepression of candidate CIC targets at transcript and protein levels was seen upon siRNA knockdown of ATXN1L. Conclusions: The interaction between CIC and ATXN1L is necessary for the repression of CIC target genes, including known oncogenes. Further research into the relationship between CIC and ATXN1L may lead potentially novel avenues of therapeutic approaches for less favorable gliomas.

Background: Vagus nerve stimulation (VNS) therapy has been widely recognized as an alternative for the treatment of drug-resistant epilepsy, although modification of antiepileptic drugs (AEDs) during VNS treatment could explain the improvement in patients. Methods: We retrospectively assessed the efficacy of VNS in 30 adult patients with epilepsy treated with >6 months of follow-up. The criteria for implantation were the following: (1) not a candidate for resective epilepsy surgery, (2) drug-resistant epilepsy, (3) impairment of quality of life, (4) no other option of treatment, and (5) patients with idiopathic generalized epilepsy who fail to be controlled with appropriate AEDs. We assessed sociodemographics, seizure etiology, seizure classification, and AEDs used during treatment with VNS. We assessed adverse effects and efficacy. Responder rate was defined as >50% seizure improvement from baseline. Results: Thirty patients (females, 18; males, 12; age, 35.1±13.3 years) were included. After 6, 12, 24, and 36 months of follow-up, the response rates were: 13/30 (43%), 13/27 (48%), 9/22 (41%), and 8/16 (50%), respectively; none was seizure free. Fifty-seven percent, 33%, 59%, and 81% of patients had changes of medication type or dose at 6, 12, 24, and 36 months respectively. In the majority of patients, the change of medication consisted of an increase in the dose of AEDs. Conclusions: Our study shows that VNS is an effective therapy, although significant changes in medications were done along with the therapy; therefore, the real effect of VNS could be controversial.