Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.

The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.

The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.

The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.

Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.

Intracranial aneurysm (IA) is an expansion of the weakened arterial wall that is often asymptomatic until rupture, resulting in subarachnoid hemorrhage. Here we describe the high prevalence of familial IA in a cohort of Newfoundland ancestry. We began to investigate the genetic etiology of IA in affected family members, as the inheritance of this disease is poorly understood.

Whole exome sequencing was completed for a cohort of 12 affected individuals from two multiplex families with a strong family history of IA. A filtering strategy was implemented to identify rare, shared variants. Filtered variants were prioritized based on validation by Sanger sequencing and segregation within the families.

In family R1352, six variants passed filtering; while in family R1256, 68 variants remained, so further filtering was pursued. Following validation by Sanger sequencing, top candidates were investigated in a set of population controls, namely, C4orf6 c.A1G (p.M1V) and SPDYE4c.C103T (p.P35S). Neither was detected in 100 Newfoundland control samples.

Rare and potentially deleterious variants were identified in both families, though incomplete segregation was identified for all filtered variants. Alternate methods of variant prioritization and broader considerations regarding the interplay of genetic and environmental factors are necessary in future studies of this disease.

Most of the implantable pulse generators (IPGs) in deep brain stimulation (DBS) used to date are non-rechargeable requiring regular replacements. IPG replacement is a minor surgical procedure, but adverse events including neurological worsening have been reported. In this study, we determine the possibility of neurological worsening after IPG replacement in Parkinson’s disease (PD) cases on chronic DBS therapy (CDT) and its electrophysiological basis along with the therapeutic interventions used to alleviate them.

This study is a retrospective chart review of PD cases on CDT followed at London Movement Disorders Centre from January 2010 to December 2016. Included cases were those who underwent one or more IPG replacement.

A total of 45 PD cases on CDT underwent 62 IPG replacements involving 121 channels. Neurological worsening was observed in 16 (35.5%) cases following 17 (27.4%) IPG replacements, all following dual-channel IPG replacements. Tremor (41.2%), speech (35.3%), and gait (23.5%) worsened most commonly. Deviation from the pre-replacement parameters including voltage and impedance resulting in change in total electrical energy delivered (TEED) was the most common electrophysiological correlate, observed in 82.4% (14/17) IPGs having neurological worsening. This included switched laterality in a dual-channel IPG. Neurological worsening in the remaining 17.6% cases was hardware-related.

Neurological worsening followed 27.4% of IPG replacements in PD cases on CDT with approximately 82.4% of these being avoidable by carefully monitoring stimulation parameters to match pre-replacement TEED values.

MR perfusion imaging is a relatively new technique that may aid in identifying recurrent tumor (RT) in those with radically treated high-grade gliomas (HGG). We aim to assess the relationship between dynamic susceptibility contrast-enhanced MR perfusion (DSC-MRP) and overall survival to establish a baseline for future research and to determine the utility of DSC-MRP as a clinical decision-making and prognostic tool.

We conducted a retrospective cohort study. Adults with pathologically confirmed HGG at the Juravinski Cancer Centre, Ontario between January 2011 and April 2014 with at least one post-treatment DSC-MRP were included. DSC-MRP was interpreted as positive or negative for tumor recurrence by experienced radiologists. The primary outcome was overall survival.

Sixty-one patients were enrolled. Median survival for patients with a positive DSC-MRP scan was 4.5 months compared with 10.2 months for those with a negative DSC-MRP scan (hazard ratio [unadjusted] = 2.51; 95% confidence interval = 1.10–5.67; p-value = 0.03). Multivariable modeling (adjusted) that included all pre-selected variables showed similar results.

Survival time in patients with HGG is generally low, and almost all patients will demonstrate RT. Our data suggest a positive DSC-MRP correlates with lower overall survival and may signify the presence of highly active RT. These results generate a hypothesis that there may be a prognostic role for the use of serial DSC-MRP for tumor surveillance. More importantly, this biomarker may aid in decision making for treatment plans and palliation.

Clinical trials with percutaneous vertebral augmentation (PVA) for intractable pain from vertebral compression fractures (VCF) have shown variable results. Variation in the outcomes may be related to poor patient selection on imaging.

To assess if PVA augmentation for osteoporotic VCF results in better improvement in pain when patients were selected based on clinical examination plus imaging vs clinical examination only.

A systematic review and meta-analysis were performed. PubMed, Embase and Cochrane Library databases were searched from 2000 to May 2018. Two reviewers independently screened and extracted data to identify randomised control trials (RCTs) on PVA for osteoporotic VCF and assessed the risk of bias. Standard systematic review and meta-analysis methods were advocated by the Cochrane Collaboration and PRISMA Statement. A total of 12 RCTs with 1110 participants met the inclusion criteria. Eight of the 10 studies (938 participants) that used imaging to confirm oedema in the target vertebral bodies showed PVA (compared to nonsurgical treatment) was effective in reducing pain (immediate term: mean difference (MD) of −1.89; 95% confidence interval −1.93 to −1.85, p < 0.001; short term: MD of −1.68; 95% CI −1.82 to −1.54, p < 0.001; intermediate term: MD of −2.04; 95% CI −2.15 to −1.94, p < 0.001 and long term: MD of −1.88; 95% CI −1.95 to −1.80, p < 0.001).

RCTs using imaging to confirm marrow oedema in the index vertebra showed an improved size effect compared to RCTs using no imaging. This benefit was observed in the immediate, short, intermediate and long term.

Brain neoplasms are the second-most prevalent cancer of childhood for which surgical resection remains the main treatment. Intraoperative MRI is a useful tool to optimize brain tumor resection. It is, however, not known whether intraoperative MRI can detect complications such as hyperacute ischemic infarcts.

A retrospective analysis of pre- and intraoperative MRIs including DWI sequence and correlation with early and 3-month postoperative MRIs was conducted to evaluate the incidence of hyperacute arterial infarct during pediatric brain tumor resection. Patient demographics, pathological type, tumor location, resection type as well as preoperative tumoral vessel encasement, evolution of the area of restricted diffusion were collected and analyzed comparatively between the group with acute infarct and the control group. Extent of the hyperacute infarct was compared to both early postsurgical and 3-month follow-up MRIs.

Of the 115 cases, 13 (11%) developed a hyperacute arterial ischemic infarct during brain tumor resection. Tumoral encasement of vessels was more frequent in the infarct group (69%) compared to 25.5% in the control group. Four cases showed additional vessel irregularities on intraoperative MRI. On early follow-up, the infarcted brain area had further progressed in six cases and was stable in seven cases. No further progression was noted after the first week post-surgery.

Hyperacute infarcts are not rare events to complicate pediatric brain tumor resection. Tumoral encasement of the circle of Willis vessels appears to be the main risk factor. Intraoperative DWI underestimates the final extent of infarcted tissue compared to early postsurgical MRI.

In 2013, a task force was developed to discuss the future of the Canadian pediatric neurology workforce. The consensus was that there was no indication to reduce the number of training positions, but that the issue required continued surveillance. The current study provides a 5-year update on Canadian pediatric neurology workforce data.

Names, practice types, number of weekly outpatient clinics, and dates of certification of all physicians currently practicing pediatric neurology in Canada were obtained. International data were used to compute comparisons between countries. National data sets were used to provide information about the number of residency positions available and the number of Canadian graduates per year. Models for future projections were developed based on published projected population data and trends from the past decade.

The number of pediatric neurologists practicing in Canada has increased 165% since 1994. During this period, wait times have not significantly shortened. There are regional discrepancies in access to child neurologists. The Canadian pediatric neurology workforce available to see outpatient consultations is proportionally less than that of USA. After accounting for retirements and emigrations, the number of child neurologists being added to the workforce each year is 4.9. This will result in an expected 10-year increase in Canadian pediatric neurologists from 151 to 200.

Despite an increase in the number of Canadian child neurologists over the last two decades, we do not predict that there will be problems with underemployment over the next decade.

This study aimed to explore student-athletes’ concussion-related knowledge and attitudes toward reporting symptoms, demographic predictors of knowledge and attitudes, and determine whether responses to the survey changed following an online educational intervention.

A total of 108 Division I student-athletes enrolled at a large southern university completed a survey evaluating knowledge regarding concussion-related terminology, symptoms and recovery trajectories, as well as attitudes toward reporting symptoms following a possible concussion. Student-athletes completed the questionnaire both 24–48 h before and one week after reviewing the educational presentation.

At baseline, participants correctly identified 72% of concussion symptoms included in the questionnaire, as well as correctly identified 75% of items related to the typical recovery trajectory post-concussion. A total of 54% of baseline attitudes toward reporting symptoms matched clinical best practices. Multiple analysis of variance (MANOVA) revealed that male sex and non-Caucasian race were associated with worse baseline knowledge of concussion symptoms. Concussion knowledge was not associated with attitudes toward reporting symptoms. Paired samples t-tests indicated that knowledge of concussion-related terminology improved modestly following the educational presentation.

Some subsets of collegiate student-athletes show relatively lower knowledge about symptoms of concussion than others. As a result, these groups may benefit from increased educational efforts to ensure they recognize when a concussion may have occurred. Additionally, as knowledge and attitudes were unrelated and the intervention had a modest effect on knowledge but not attitudes, future work should explore interventions that are designed to directly alter attitudes.