Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.

Research in human subjects is at the core of achieving improvements in health outcomes. For clinical trials, in addition to the peer review of the results before publication, it is equally important to consider whether the trial will be conducted in a manner that generates data of the highest quality and provides a measure of safety for the participating subjects. In Canada, there is no definitive legislation that governs the conduct of research involving human subjects, but a network of regulations at different levels does provide a framework for both principal investigators and sponsors. In this paper, we provide an overview of the federal, provincial and institutional legislation, guidelines and policies that will inform readers about the requirements for clinical trial research. This includes a review of the role of the Food and Drug Regulations under the Food and Drugs Act and the Tri-Council Policy Statement (TCPS2), an overview of provincial legislation across the country, and a focus on selected policies from institutional research ethics boards and public health agencies. Many researchers may find navigation through regulations frustrating, and there is a paucity of information that explains the interrelationship between the different regulatory agencies in Canada. Better understanding the process, we feel, will facilitate investigators interested in clinical trials and also enhance the long-term health of Canadians.

In this article, we conduct a review of introduced and enacted youth concussion legislation in Canada and present a conceptual framework and recommendations for future youth sport concussion laws. We conducted online searches of federal, provincial, and territorial legislatures to identify youth concussion bills that were introduced or successfully enacted into law. Internet searches were carried out from July 26 and 27, 2016. Online searches identified six youth concussion bills that were introduced in provincial legislatures, including two in Ontario and Nova Scotia and one each in British Columbia and Quebec. One of these bills (Ontario Bill 149, Rowan’s Law Advisory Committee Act, 2016) was enacted into provincial law; it is not actual concussion legislation, but rather a framework for possible enactment of legislation. Two bills have been introduced in federal parliament but neither bill has been enacted into law. At present, there is no provincial or federal concussion legislation that directly legislates concussion education, prevention, management, or policy in youth sports in Canada. The conceptual framework and recommendations presented here should be used to guide the design and implementation of future youth sport concussion laws in Canada.

Background: Computer-assisted navigation (CAN) may guide spinal instrumentation, and requires alignment of patient anatomy to imaging. Iterative-Closest-Point algorithms register anatomical and imaging datasets, which may fail in the presence of significant geometric congruence leading to inaccurate navigation. We computationally quantify geometric congruence in posterior spinal exposures, and identify predictors of potential navigation inaccuracy. Methods: Midline posterior exposures were performed from C1-S1 in four human cadavers. An optically-based CAN generated surface maps of the posterior elements at each level. Maps were reconstructed to include bilateral hemilamina, or unilateral hemilamina with/without the base of the spinous process. Maps were fitted to symmetrical geometries (cylindrical/spherical/planar) using computational modelling, and the degree of model fit quantified. Results: Increased cylindrical/spherical/planar symmetry was seen in the subaxial cervical spine relative to the high-cervical and thoracolumbar spine (p<0.001). Inclusion of the base of the spinous process decreased symmetry independent of spinal level (p<0.001). Registration with bilateral vs. unilateral hemilamina did not significantly reduce geometric symmetry. Conclusions: Geometric congruence is most evident at C1 and the subaxial cervical spine, warranting greater vigilance in navigation accuracy verification. At all levels, inclusion of the base of the spinous process in unilateral registration decreases the likelihood of geometric symmetry and navigation error.

Augmented reality (AR) superimposes computer-generated virtual objects onto the user’s view of the real world. Among medical disciplines, neurosurgery has long been at the forefront of image-guided surgery, and it continues to push the frontiers of AR technology in the operating room. In this systematic review, we explore the history of AR in neurosurgery and examine the literature on current neurosurgical applications of AR. Significant challenges to surgical AR exist, including compounded sources of registration error, impaired depth perception, visual and tactile temporal asynchrony, and operator inattentional blindness. Nevertheless, the ability to accurately display multiple three-dimensional datasets congruently over the area where they are most useful, coupled with future advances in imaging, registration, display technology, and robotic actuation, portend a promising role for AR in the neurosurgical operating room.

Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.

During the “DBS Canada Day” symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to discuss three main questions on target selection for deep brain stimulation (DBS) of patients with Parkinson’s disease (PD). First, is the subthalamic nucleus (STN) or the globus pallidus internus (GPi) the ideal target? In summary, both targets are equally effective in improving the motor symptoms of PD. STN allows a greater medications reduction, while GPi exerts a direct antidyskinetic effect. Second, are there further potential targets? Ventral intermediate nucleus DBS has significant long-term benefit for tremor control but insufficiently addresses other motor features of PD. DBS in the posterior subthalamic area also reduces tremor. The pedunculopontine nucleus remains an investigational target. Third, should DBS for PD be performed unilaterally, bilaterally or staged? Unilateral STN DBS can be proposed to asymmetric patients. There is no evidence that a staged bilateral approach reduces the incidence of DBS-related adverse events.

Background: Hyperacute stroke is a time-sensitive emergency for which outcomes improve with faster treatment. When stroke systems are accessed via emergency medical services (EMS), patients are routed to hyperacute stroke centres and are treated faster. But over a third of patients with strokes do not come to the hospital by EMS, and may inadvertently arrive at centres that do not provide acute stroke services. We developed and studied the impact of protocols to quickly identify and move “walk-in” patients from non-hyperacute hospitals to regional stroke centres (RSCs). Methods and Results: Protocols were developed by a multi-disciplinary and multi-institutional working group and implemented across 14 acute hospital sites within the Greater Toronto Area in December of 2012. Key metrics were recorded 18 months pre- and post-implementation. The teams regularly reviewed incident reports of protocol non-adherence and patient flow data. Transports increased by 80% from 103 to 185. The number of patients receiving tissue plasminogen activator (tPA) increased by 68% from 34 to 57. Total EMS transport time decreased 17 minutes (mean time of 54.46 to 37.86 minutes, p<0.0001). Calls responded to within 9 minutes increased from 34 to 59%. Conclusions: A systems-based approach that included a multi-organizational collaboration and consensus-based protocols to move patients from non-hyperacute hospitals to RSCs resulted in more patients receiving hyperacute stroke interventions and improvements in EMS response and transport times. As hyperacute stroke care becomes more centralized and endovascular therapy becomes more broadly implemented, the protocols developed here can be employed by other regions organizing patient flow across systems of stroke care.

Objectives: To assess the etiology of cerebrospinal fluid (CSF) pleocytosis in critical care patients with seizure(s) or status epilepticus (SE). Many previous studies, some performed decades ago, concluded that CSF pleocytosis may be entirely attributable to seizure activity. Methods: We undertook a retrospective chart review of adult patients with an admitting or acquired diagnosis of seizure(s) or SE in critical care units at the Winnipeg Health Sciences Centre between 2009 and 2012. Patients were identified through a critical care information database at a tertiary care center. We limited our study to patients who had lumbar punctures at our center within 5 days of seizure(s) or SE. Results: Of 426 patients with seizures in critical care units, 51 met the inclusion criteria. Seizure subtypes included focal seizures (5 or 10%), generalized seizures (14 or 27%), and SE (32 or 63%). Twelve (seven with SE) of the 51 (24%) were found to have CSF pleocytosis. A probable etiological cause for the CSF pleocytosis was identified in all 12 cases. Conclusions: We conclude that seizures do not directly induce a CSF pleocytosis. Instead, the CSF pleocytosis more likely reflects the underlying acute or chronic brain process responsible for the seizure(s). This was not readily apparent in early studies without magnetic resonance imaging (MRI) of the brain and currently available laboratory investigations. An etiological cause of CSF pleocytosis must always be sought when patients present with seizures and it should never be assumed that seizures are the cause.

During the “DBS Canada Day” symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to share their knowledge regarding deep brain stimulation (DBS) management of movement disorders in three domains: (1) the programming algorithms, (2) the necessary team to run a neurosurgery program, and (3) the appropriate scales to better define in a more comprehensive fashion the effect of the brain surgery. Each presentation was followed by an open discussion, and this article reports on the conclusions of this meeting on these three questions. Concerning programming, the role of the pulse width and the switching off of the stimulation at night for thalamic stimulation for the control of tremor have been discussed. The algorithms proposed in the literature for programming in Parkinson’s disease (PD) need validation. In dystonia, the use of monopolar vs bipolar parameters, the use of low vs high frequencies and the use of smaller versus larger pulse widths all need to be examined properly. Concerning the necessary team to run a neurosurgical program, recommendations will follow the suggestions for standardized outcome measures. Regarding the outcome measures for DBS in PD, investigations need to focus on the non-motor aspects of PD. Identifying which nonmotor symptoms respond to DBS would allow a better screening before and satisfaction postoperatively. There is an important need for more data to determine the optimal programming protocol and the standard measures that should be performed routinely by all centers.

Objective Chronic cerebrospinal venous insufficiency (CCSVI) has been hypothesized to be a risk factor for multiple sclerosis (MS). Venoplasty has been proposed as a treatment for CCSVI. The aim of our study was to gain a better understanding of the “real-world” safety and longitudinal effectiveness of venoplasty Methods: British Columbia residents who self-reported having had venoplasty and consented to participate in the study were interviewed and followed for up to 24 months post-therapy using standardized structured questionnaires Results: Participants reported procedure-related complications (11.5%) and complications within the first month after the procedure (17.3%). Initially, more than 40% of participants perceived that the venoplasty had had positive effects on their health conditions, such as fatigue, numbness, balance, concentration/memory and mobility. However, this improvement was not maintained over time Conclusions: Follow-up patient-reported outcomes indicated that the initial perception of the positive impact of venoplasty on the health conditions of MS patients was not sustained over time. In addition, venoplasty was not without associated morbidity.

Objective: Prospective memory (PM) is a cognitive function defined as the ability to perform an intention at an appropriate moment in the future. In the aging population, PM is essential for maintaining independent daily living. Introduced as a simple and quick way to assess PM in clinical settings, the envelope task has to date received very limited empirical and practical interest. Methods: The present study investigated the task’s clinical utility in detecting PM impairment in a sample composed of 49 healthy older adults (OA), 41 patients with Alzheimer’s disease, and 64 individuals with amnestic and nonamnestic mild cognitive impairment (MCI) of heterogeneous etiology: 17 of idiopathic nature, 20 presenting an idiopathic rapid-eye movement sleep behaviour disorder, and 27 patients diagnosed with idiopathic Parkinson’s disease. Results: The envelope task was highly sensitive and specific in discriminating Alzheimer’s disease patients from OA. Although it was specific in distinguishing MCI individuals from OA, its sensitivity was modest, especially in patients presenting a nonamnestic MCI subtype. Conclusions: Given its high specificity and simple low-cost administration procedure, the envelope task is a promising instrument for clinicians who seek to rapidly assess PM impairment in their daily practice.

Background: Resting state functional connectivity (RSFC) in the fronto-parietal network (FPN) has been associated with cognitive ability. For this reason, it was hypothesized that RSFC connectivity of the FPN would be related to cognition in patients with diffuse glioma. To assess this relationship, pre-operative cognitive status was correlated to patient specific connectivity within the FPN. Further, we assessed whether RSFC could predict neuropsychological outcome following surgery Methods: Sixteen patients with diffuse glioma underwent neuropsychological assessment and pre-operative task and resting state fMRI. Thirteen had post-operative cognitive assessment at one-month post-surgery. RSFC in a subject-specific FPN was correlated with pre- and post-operative cognitive scores. Results: Higher connectivity within the FPN was associated with lower composite cognitive scores, while higher connectivity of the parietal node of the tumor-affected hemisphere was associated with lower fluid cognition but not crystallized cognition. Higher connectivity values between the parietal node of the healthy hemisphere and the rest of the FPN was associated with better neuropsychological outcome one month after surgery. Conclusions: RSFC between key nodes of the FPN is associated with cognitive performance in patients with diffuse glioma and is a promising biomarker for cognitive outcome following surgery.