Premature mortality among epilepsy patients is well recognized. Except a few identifiable causes of unnatural death, more than half of the epilepsy related death remains unexplained after extensive workup. These cases are classified as sudden unexpected death in epilepsy (SUDEP). SUDEP incidence varies significantly depending on the population, the methods documenting cause of death and the availability of Neuropathological examination. An accurate diagnosis of the cause of death is needed for epilepsy related death. The goal of this study is to present the relevant clinical data, the general autopsy and Neuropathology findings of epilepsy related death investigated in London Health Sciences Center during the period of 2000 to 2011. We identified 71 cases with known history of chronic epilepsy. In the 29 cases of epilepsy associated death, the causes of death have been classified as cardiac, pulmonary, accidental (e.g. drowning), toxic (e.g. drug overdose) and non-related causes. Forty two cases are considered to be SUDEP, and were categorized according to the recently proposed SUDEP Definition and Classification. Half of the SUDEP cases have no specific Neuropathological findings. The most common identifiable lesions in SUDEP cases are perinatal/neonatal destructive lesions (29%), hippocampal sclerosis (24%), and focal cortical dysplasia (20%). These are followed by neuronal heterotopia (9%), previous head trauma (9%), and cavernoma (5%).

Objectives: To evaluate the attitudes and perceptions of psychiatrists and psychiatry residents regarding neurosurgical procedures for treating psychiatric disorders and to identify potential barriers to patient referral. Methods: A survey consisting of 25 questions was created using SurveyMonkey and was distributed to psychiatrists and psychiatry residents in Quebec. The study was approved by the McGill University Health Center’s Research Ethics Board. Descriptive statistics and Friedman’s test were performed using SPSS software. Results: A total of 99 participants, including 64 residents and 35 psychiatrists, completed more than 75% of the survey and were included in data analysis. Overall, participants were significantly (p < 0.0005) more comfortable in referring patients suffering from treatment-resistant obsessive–compulsive disorder than from treatment-resistant major depressive disorder and preferred to refer patients for deep brain stimulation (DBS) rather than for anterior cingulotomy/capsulotomy (AC). Only 11.43% of psychiatrists had ever referred a patient for AC or DBS, and 34.69% of respondents felt that these procedures were dangerous. Lack of knowledge (82.83%) was viewed as the principal limiting factor, and 57.58% of respondents identified ≥6 different barriers to patient referral. The majority of participants (69.39%) were interested in improving their knowledge on psychiatric neurosurgery, and 82.65% felt that this subject should be included in the psychiatry residency curriculum. Conclusion: Overall, participants acknowledged having many limitations to referring patients for neurosurgical interventions. While informative conferences discussing neuromodulation/neuroablation could easily address many barriers, further studies are required to assess how these could change attitudes and patterns of referral.

Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length. Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors. Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001). Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.

Background: As with other specialties, Royal College of Physicians and Surgeons of Canada (RCPSC) trainees in Neurosurgery have anecdotally had challenges securing full-time employment. This study presents the employment status, research pursuits, and fellowship choices of neurosurgery trainees in Canadian programs. Methods: RCPSC neurosurgery trainees (n = 143) who began their residency training between 1998 and 2008 were included in this study. Associations between year of residency completion, research pursuits, and fellowship choice with career outcomes were determined by Fisher’s exact test (p < 0.05, statistical significance). Results: In 2015, 60% and 26% of neurosurgery trainees had permanent positions in Canada and the USA, respectively. Underemployment, defined as locum and clinical associate positions, pursuit of multiple unrelated fellowships, unemployment, and career change to non-surgical career, was 12% in 2015. The proportion of neurosurgery trainees who had been underemployed at some point within 5 years since residency completion was 20%. Pursuit of in-folded research (MSc, PhD, or non-degree research greater than 1 year) was significantly associated with obtaining full employment (94% vs. 73%, p = 0.011). However, fellowship training was not significantly associated with obtaining full employment (78% vs. 75%, p = 1.000). Conclusions: Underemployment in neurosurgery has become a significant issue in Canada for various reasons. Pursuit of in-folded research, but not fellowship training, was associated with obtaining full employment.

Background: Primary Progressive Aphasia (PPA) involves an isolated impairment of language function at disease onset. The cholinergic system is implicated in language and cholinergic deficits are seen in brains of individuals with PPA. One major source of cholinergic innervation is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). We quantified cholinergic neurons in the NBM and NSP of PPA and controls. Also explored was whether individuals with PPA who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Methods: Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n=5) and PPA (n=5) brains. Choline acetyltransferase immunohistochemical staining labelled cholinergic neurons, quantified using Neurolucida software. Results: Compared to matched controls, PPA showed reduction of cholinergic neurons in the NBM, t(4) = 4.224, p = 0.013; Cohen’s d=1.89 and the NSP, t(4) = 4.013, p = 0.016; Cohen’s d= 1.79. The average percent of cholinergic neuronal loss was higher in the NSP (64.66%) compared to NBM (17.66%). Conclusions: Regardless of underlying pathology, all cases presenting with PPA showed marked loss of cholinergic neurons in the NSP providing further evidence for the importance of this nucleus in language function.

Objective: To develop a detailed profile of individuals living with migraine in Canada. Such a profile is important for planning and administration of services. Methods: The 2011–2012 Survey of Living with Neurological Conditions in Canada (SLNCC), a cross-sectional community-based survey, was used to examine a representative sample of migraineurs (N = 949) aged 15 years and older. Several health-related variables were examined (e.g., general health, health utility index (HUI) [a measure of health status and health-related quality of life, where dead = 0.00 and perfect health = 1.00], stigma, depression, and social support). Respondents were further stratified by sex, age, and age of migraine onset. Weighted overall and stratified prevalence estimates and odds ratios, both with 95% CIs, were used to estimate associations. Results: Overall, males had poorer health status compared with females (e.g., mean HUI was 0.67 in males vs. 0.82 in females; men had over two times the odds of their migraine limiting educational and job opportunities compared with females). Poorer health-related variables were seen in the older age groups (35–64 years/≥65 years) compared with the 15–34-year age group. There were no differences between those whose migraine symptoms began before versus after the age of 20 years. Conclusions: In this Canadian sample, migraine was associated with worse health-related variables in men compared with women. However, both men and women were significantly affected by migraine across various health-related variables. Thus, it is important to improve clinical and public health interventions addressing the impact of migraine across individuals of all ages, sexes, and sociodemographic backgrounds.

Hypochondroplasia, achondroplasia, and thanatophoric dysplasia are related at the molecular level, all caused by fibroblast growth factor receptor 3 (FGFR3) gene mutations. They differ in severity. FGFR3 has critical roles in fibroblast growth factor (FGF) signalling pathways during bone growth and cerebral cortical development. Mutations of the FGFR3 gene lead to constitutive activation of FGFR3. The well-described brain malformation in thanatophoric dysplasia is characterized by gross abnormalities of temporal lobe patterning and severe dysplasia of the hippocampus. Experimental models suggest that increased proliferation, abnormal migration, and decreased apoptosis are involved. However, reports of the brain findings in hypochondroplasia are based solely on radiologic imaging.

We present the neuropathology of a 44 year-old man with hypochondroplasia, epilepsy, and significant intellectual disability. The temporal lobes are enlarged, prominent fissures traverse the inferior temporal surface, and the hippocampus is abnormally folded. Microscopically, the dentate gyrus is variably small or thin and is located near the edge of a gyrus. Ammon’s horn is displaced and meandering. Subicular-like clusters are profuse. Complex gyri resemble microgyria. White matter forms a subpial border in some gyri. In summary: medial temporal lobe dysgenesis.

This individual also had many autistic features including stereotypies and head banging. The latter could explain another surprising set of brain abnormalities unrelated to the presumed FGFR3-related syndrome.

Background: The Montreal Cognitive Assessment (MoCA) is a cognitive screening tool known to accurately measure mild cognitive impairment (MCI) in many different neurological populations. Objective: We aimed to determine whether a sport-related concussion (SRC) history and other concussion modifiers influence global cognitive function in high-performance athletes. Methods: A cross-sectional study of 326 varsity and national team athletes aged 18–36 years was completed at the University of Calgary Sports Medicine Clinic, Calgary, Alberta, Canada. Logistic regression analysis was used to examine the association between the total MoCA score, MoCA subscales, and number of previous SRC, adjusting for age, sex, sport participation (SP), and concussion modifiers. Results: Athletes with a history of three or more SRC were 5.36 times more likely to score less than 26/30 on the MoCA (the cutoff for MCI) compared to athletes with two or less SRC (p = 0.02). Males were 2.23 times more likely to have MCI than females (p = 0.0004). There was a significant relationship between the number of previous concussions and the MoCA subscales of attention (p = 0.05) and abstraction (p = 0.003). Age, SP, and concussion modifiers (migraine, depression, anxiety, and attention deficit and hyperactivity disorder) did not influence the relationship between MoCA and previous concussion history. Conclusion: In the appropriate clinical context, cognitive screening with the MoCA may benefit clinical care in athletes with multiple previous SRC, but should not replace a full neuropsychological assessment. Thus, further research is needed to compare the MoCA to full neuropsychological assessments in this population.

Objective: To summarize the findings of randomized controlled trials (RCTs) on the efficacy and safety of vitamins and minerals for migraine prophylaxis. Methods: We systematically searched bibliographic databases and relevant websites for parallel and crossover RCTs reporting efficacy and/or safety of vitamins and/or minerals for migraine prophylaxis. Our primary outcomes were migraine frequency (number of attacks) and duration (hours). Secondary outcomes were severity (intensity), days with migraine, and adverse events. Meta-analysis was conducted when analyzable data were available from at least two trials. Results: Eighteen placebo-controlled trials met our eligibility criteria. Only coenzyme Q10 and magnesium contributed to meta-analyses. In adults, compared with placebo, coenzyme Q10 did not significantly decrease migraine frequency (mean difference (MD) −0.44 (−2.14 to 1.26); I2 53%; 2 trials; 97 participants; moderate strength of the evidence), duration (MD −1.97 (−4.82 to 0.87); I2 0%; 2 trials; 97 participants; moderate strength of the evidence), or severity (ratio of means (RoM) −0.05 (−0.20 to 0.11); I2 0%; 2 trials; 97 participants). In adults, compared with placebo, magnesium did not significantly decrease migraine severity (RoM −0.17 (−0.36 to 0.02); I2 48%; 3 trials; 226 participants; low strength of the evidence). Meta-analysis of other vitamins and minerals, and other outcomes were not feasible due to a lack of sufficiently reported data. Conclusions: Based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and safety of vitamins and minerals for migraine prophylaxis.

The area postrema (AP) in the caudal 4th ventricular floor is unique, highly vascular without blood/brain or /CSF barrier. In addition to its function as the vomiting centre, several other important functions are: part of the circumventricular organs for vasomotor and angiotensin II regulation; a role in neuromyelitis optica related to aquaporin-4; contributor to fetal and postnatal somatic growth. Functions are immature at birth.

The purpose of this study was to demonstrate AP neuronal/synaptic/glial maturation in normal fetuses and 3 AP tumours. Transverse sections of the caudal 4th ventricle of 18 normal human fetal brains at autopsy, 6 to 40 weeks were examined; also 3 infants 3-18mos; 2 children. A battery of immunocytochemical neuronal and glial markers: MAP2; calretinin; synaptophysin; vimentin; nestin; GFAP; S-100β protein; were applied to paraffin sections. Two children with AP tumours and one with neurocutaneous melanocytosis, all with pernicious vomiting, were studied. In normal fetuses, AP neurons exhibited cytological maturity and well-formed synaptic circuitry by 14wk gestation. Size/volume increase was disproportionately greater than brainstem growth in 2nd and 3rd trimesters and postnatally. Astrocytes co-expressed vimentin/GFAP but glia were best demonstrated by S-100β protein. Ependyma over the AP in fetuses is simple cuboidal, adjacent to pseudostratified columnar of the 4th ventricular floor. Melanocytes infiltrated AP in the toddler with pernicious vomiting; 2 children had primary AP pilocytic astrocytomas. Though AP is cytologically mature by 14wk, growth increases and functions mature into the postnatal months. We recommend that AP neuropathology include synaptophysin and S-100β at autopsy if AP dysfunction suspected.

Background: There is currently no accepted classification of recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus and develop a clinical and pathophysiological classification for recessive ataxias. Methods: The work of this task force was based on a scoping systematic review of the literature that identified recessive disorders characterized primarily by a cerebellar motor syndrome and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. Results: We identified 59 disorders that are classified as primary recessive ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. The primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders in which ataxia is a secondary feature. Conclusions: This classification is based on a scoping systematic review of the literature and results from a sconsensus among a panel of international experts. It promotes a unified understanding of recessive cerebellar disorders for clinicians and researchers.

Background and Objectives: Federal and provincial governments in Canada are promoting provincial legislation to prevent and manage sport-related concussions (SRCs). The objective of this research was to determine the incidence of concussions in high school sport, the knowledge of the signs, symptoms, and consequences of SRC, and how likely student athletes are to report a concussion. Methods: A cross-sectional survey of athletes (N = 225) from multiple sports in five high schools in one Manitoba school division was conducted. Results: Participants in this study were well aware of the signs, symptoms, and consequences of SRC. Cognitive and emotional symptoms were the least recognized consequences. SRC is prevalent in high schools in both males and females across all sports. Of the 225 respondents, 35.3% reported having sustained an SRC. Less than half (45.5%) reported their concussion. Athletes purposely chose not to report a concussion in games (38.4%) and practices (33.8%). Two major barriers to reporting were feeling embarrassed (3.4/7) and finding it difficult (3.5/7) to report. There was, however, strong agreement (Mean 5.91/7, SD 0.09) when asked if they intend to report a concussion should they experience one in the future. Conclusions: The results suggest that high school athletes would benefit from more SRC education. Coaches and team medical staff must be trained to be vigilant for the mechanism, signs, and symptoms of injury in both game and practice situations. This study will also inform the implementation of pending legislation in Manitoba and perhaps other provinces in Canada.

Background: A Will, Power of Attorney, and Advanced Healthcare Directive are critical to guide decision-making in patients with dementia. We identified characteristics that are associated with the existence of these documents in patients who presented to a rural and remote memory clinic (RRMC). Methods: Ninety-five consecutive patients were included in this study. Patients and caregivers completed questionnaires on initial presentation to the RRMC and patients were asked if they had legal documents. Patients also completed neuropsychological testing. Statistical analysis (t-test and χ2 test) was performed to identify significant variables. Results: Seventy (73.7%) patients had a Will, 62 (65.3%) had a Power of Attorney, and 21 (22.1%) had an Advanced Healthcare Directive. Having a Will was associated with good quality of life (p = 0.001), living alone or with a spouse or partner only (p = 0.034), poor verbal fluency (p = 0.055), and European ethnicity (p = 0.028). Factors associated with having a Power of Attorney included good quality of life (p = 0.031), living alone or with a spouse or partner only (p = 0.053), and poor verbal fluency (p = 0.015). Old age (p = 0.015), poor verbal fluency (p = 0.023), and greater severity of cognitive and functional impairment (p = 0.023) were associated with having an Advanced Healthcare Directive. Conclusions: Our results indicate that poor quality of life, good performance on verbal fluency, Indigenous ethnicity, and living with others are associated with a lower likelihood of legal documents in patients with dementia. These factors can help physicians identify patients at risk of leaving their legal affairs unattended to. Physicians should discuss the creation of legal documents early on in patients with signs of dementia.

Objective: Focal cortical dysplasia (FCD) is a common cause of refractory, focal onset epilepsy in children. Interictal, scalp electroencephalograph (EEG) markers have been associated with these pathologies and epilepsy surgery may be an option for some patients. We aim to study how scalp EEG and magnetic resonance imaging (MRI) markers of FCD affect referral of these patients for surgical evaluation. Methods: A single-center, retrospective review of children with focal onset epilepsy. Patients were included if they were between 1 month and 18 years of age, had focal onset seizures, prolonged scalp EEG monitoring, and an MRI conducted after 2 years of age. Statistics were carried out using the chi-squared and student’s t-test, as well as a logistic regression model. Results: Sixty-eight patients were included in the study. Thirty-seven of these patients were referred to a comprehensive pediatric epilepsy program (CPEP) for surgical evaluation, and of these 22% showed FCD EEG markers, 32% FCD MRI markers, and 10% had both. These markers were also present in patients not referred to a CPEP. The MRI markers were significantly associated with CPEP referral, whereas EEG markers were not. Neither marker type was associated with epilepsy surgery. Conclusion: This study found that children with focal onset epilepsy were more likely to be referred for surgical evaluation if they were medically refractory, or were diagnosed with FCD or tumor on MRI. Scalp EEG markers of FCD were not associated with CPEP referral. The online tool CASES may be a useful physician guide for identifying appropriate children for epilepsy surgery referral.