The Province of Ontario recognized the pressing need to improve the understanding, diagnosis, and treatment of brain disorders. It also recognized that maximizing the existing strengths through a province-wide integrated approach was a pivotal mechanism. To achieve this, the Province established the Ontario Brain Institute. The goal of this article is to introduce the elements of the Ontario Brain Institute to the neuroscience community: the motivation for establishing it, the philosophy behind its creation, the principles guiding its development, the rapid evolution of its functional structure, the tools available to achieve its vision, and the management structure to ensure success. The singular goal of the Province and the Ontario Brain Institute is a comprehensive system that assures that basic research is embedded in the clinical system and is facilitating product development to accelerate benefits to both health and the economy of health: science with impact.

Background: Community stroke rehabilitation teams (CSRTs) provide a community-based, interdisciplinary approach to stroke rehabilitation. Our objective was to assess the effectiveness of these teams with respect to client outcomes. Methods: Functional, psychosocial, and caregiver outcome data. were available at intake, discharge from the program, and six-month follow-up. Repeated measures analysis of covariance was performed to assess patient changes between time points for each outcome measure. Results: A total of 794 clients met the inclusion criteria for analysis (54.4% male, mean age 68.5±13.0 years). Significant changes were found between intake and discharge on the Hospital Anxiety and Depression Scale total score (p=0.017), Hospital Anxiety and Depression Scale Anxiety subscale (p<0.001), Functional Independence Measure (p<0.001), Reintegration to Normal Living Index (p=0.01), Bakas Caregiver Outcomes Scale (p<0.001), and Caregiver Assistance and Confidence Scale assistance subscale (p=0.005). Significant gains were observed on the strength, communication, activities of daily living, social participation, memory, and physical domains of the Stroke Impact Scale (all p<0.001). These improvements were maintained at the 6-month follow-up. No significant improvements were observed upon discharge on the memory and thinking domain of the Stroke Impact Scale; however, there was a significant improvement between admission and follow-up (p=0.002). All significant improvements were maintained at the 6-month follow-up. Conclusions: Results indicate that the community stroke rehabilitation teams were effective at improving the functional and psychosocial recovery of patients after stroke. Importantly, these gains were maintained at 6 months postdischarge from the program. A home-based, stroke-specific multidisciplinary rehabilitation program should be considered when accessibility to outpatient services is limited.

Background: Atrial fibrillation (AF) is a cause of ischemic stroke and is associated with recurrence and with acute multi-vessel territory non lacunar stroke. Many cryptogenic strokes could be secondary to undiagnosed paroxystic AF. As left atrium (LA) dilatation is a risk factor of AF, we sought to determine if moderate or severe LA dilatation was associated with multiple vascular territory infarcts on magnetic resonance imaging (MRI) in patients with acute ischemic stroke without known AF. Normal LA diameter values are ≤4.0 cm for men and ≤3.8 for women. Methods: Patients who presented at our center between 2006 and 2011 with a diagnosis of acute ischemic stroke (AIS) or transient ischemick attack (TIA) who had a transthoracic echocardiography and a brain MRI were included. Patients with known or de novo AF diagnosed within 3 months of the event were excluded. The main outcome was the presence of acute multi-vessel territory infarct(s) on MRI.Results: 356 patients were included. The mean LA diameter was 37 mm in the control group (normal or mildly dilated LA) and 49 mm in those with moderately to severely enlarged LA (p<0.001). More patients in the LA dilatation group met the main outcome (20% vs 6%; OR 3.89; 95% CI 1.32-11.43; p=0.0014). Conclusions: LA dilatation (at least moderate) is associated with acute non lacunar multiple vascular territory infarcts on MRI in patients with AIS or TIA without known AF or a confirmed diagnosis of AF. Further studies are necessary to determine if this population might benefit from anticoagulation therapy.

Background: Recanalization rates and patient outcomes in acute occlusion of the carotid terminus have previously been poor. The use of stent-retrievers has resulted in better recanalization and patient outcomes. We sought to compare outcomes in patients treated with stent-retrievers to outcomes in older techniques. Methods: We retrospectively compared a stent-retriever cohort to a historical cohort. We evaluated recanalization rates and good outcomes (defined as mRS < 2 at 30 days or 10 point drop in NIHSS). Results: There were twenty patients treated with stent-retrievers versus nine without. The recanalization rate in patients treated with stent retrievers was significantly higher than that of other modalities (90% vs 33%, p=0.004). Good outcomes were significantly higher in the stent retriever cohort (70% vs 22%, p=0.041). Conclusion: The use of stent-retrievers in patients with carotid “T” occlusions shows promise in comparison to older techniques. A randomized trial comparing stent-retriever therapy to IV thrombolysis is warranted to determine the efficacy of this new generation of devices.

Background: Brain injury after intracerebral hemorrhage (ICH) arises from numerous contributors, of which some also play essential roles. Notably, thrombin production, needed to stop bleeding, also causes acute cell death and edema. In some rodent models of ICH, peri-hematoma neurons die over weeks. Hence we evaluated whether thrombin is responsible for this chronic degeneration. Functional impairments after ICH also result from sub-lethal damage to neurons, especially the loss of dendrites. Thus, we evaluated whether thrombin infusion alone, a reductionist model of ICH, causes similar injury. Methods: Adult rats had a modest intra-striatal infusion of thrombin (1 U) or saline followed by a behavioral test, to verify impairment, 7 days later. After this they were euthanized and tissue stained with Golgi-Cox solution to allow the assessment of dendritic morphology in striatal neurons. In a second experiment, rats survived 7 or 60 days after thrombin infusion in order to histologically determine lesion volume. Results: Thrombin caused early cell death and considerable atrophy in surviving peri-lesion neurons, which had less than half of their usual numbers of branches. However, total tissue loss was comparable at 7 (24.1 mm3) and 60 days (25.6 mm3). Conclusion: Thrombin infusion causes early cell death and neuronal atrophy in nearby surviving striatal neurons but thrombin does not cause chronic tissue loss. Thus, the chronic degeneration found after ICH in rats is not simply and solely due to acute thrombin production. Nonetheless, thrombin is an important contributor to behavioral dysfunction because it causes cell death and substantial dendritic injury.

Background: Postgraduate neurosurgical education is undergoing significant reform, including transition to a competency-based training model. To support these efforts, the purpose of this study was to determine neurosurgical graduates’ and program directors’ (PDs) opinions about graduates’ level of competence in reference to the 2010 Royal College Objectives of Training in Neurosurgery. Methods: An electronic survey was distributed to Canadian neurosurgery PDs and graduates from 2011. The questionnaire addressed graduates’ abilities in nonprocedural knowledge and skills, CanMEDS roles, proficiency with core neurosurgical procedures and knowledge of complex neurosurgical techniques. Results: Thirteen of 22 (59%) graduate and 17/25 (65%) PD surveys were completed. There were no significant differences between PD and graduate responses. Most respondents agreed that these graduates possess the knowledge and skills expected of an independently practicing neurosurgeon across current objectives of training. A small proportion felt some graduates did not achieve this level of proficiency on specific vascular, functional, peripheral nerve and endoscopic procedures. This was partially attributed to limited exposure to these procedures during training and perceptions that some techniques required fellowship-level training. Conclusions: Graduating neurosurgical residents are perceived to possess a high level of proficiency in the majority of neurosurgical practice domains. Inadequate exposure during training or a perception that subspecialists should perform some procedures may contribute to cases where proficiency is not as high. The trends identified in this study could be monitored on an ongoing basis to provide supplemental data to guide curricular decisions in Canadian neurosurgical training.

Background: Cognitive dysfunction is a common complaint associated with obstructive hydrocephalus. The purpose of this study was to determine the effect of endoscopic third ventriculostomy (ETV) on the neuropsychological outcome in patients presenting with cognitive decline and obstructive hydrocephalus. Methods: A retrospective review of patients who underwent ETV at the University of Calgary and had both pre and post operative neuropsychological testing, was completed. Presenting clinical features, etiology of hydrocephalus and ventricle size utilizing frontal occipital horn ratio was obtained. Outcomes and complications of the ETV were recorded. Detailed measures of intelligence, attention and concentration, executive function, visual and verbal memory, language functions and fine motor skills were completed. Post treatment change was determined utilizing Reliable Change Index. Results: A total of 13 patients were identified. Etiology of the hydrocephalus was aqueductal stenosis in 8 and tectal glioma in 4. The majority of patients (11 of 13, 85%) demonstrated cognitive dysfunction at the borderline (≤1 SD) or impairment level (≤1.5 SDs) in at least one domain. Nine patients (69%) showed reliable improvement in at least one cognitive domain. The greatest improvement was seen with visual memory (42%). One quarter to one third of patients demonstrated improvement on tests of intelligence quotient, verbal memory, attention and concentration, and executive function. Two patients declined in executive functioning. Ventricle size improved in eight patients. Conclusions: ETV is a safe effective procedure, capable of producing reliable improvements in cognitive dysfunction with hydrocephalus. Patients with cognitive complaints alone may benefit from ETV.

Background: Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR). Methods: This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada. Results: Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022). Conclusions: This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.

Background: Anti–John Cunningham (JCV) antibodies have been detected in approximately 50% to 60% of multiple sclerosis (MS) patients. Age, sex, and geographic location have been associated with seroprevalence differences. We describe anti-JCV antibody prevalence in the Canadian cohort of patients enrolled in the JCV Epidemiology in MS study. Methods: This cross-sectional multicenter study evaluated the effects of demographic and disease characteristics on anti-JCV antibody seroprevalence in MS patients irrespective of disease type and treatment. A single blood sample was collected for analysis of anti-JCV antibodies using a two-step enzyme-linked immunosorbent assay (ELISA). Chi-square and logistic regression tests were used to determine significance. Results: A total of 4198 Canadian MS patients participated in the study; the overall anti-JCV antibody prevalence was 56.3% (95% confidence interval: 54.8% to 57.8%). Seroprevalence was significantly associated with age (increasing from 45% in young to 61% in those >60 years), sex, and region (p<0.0001 for age and sex; p=0.005 for region). No significant differences in anti-JCV antibody prevalence were associated with race, MS disease type and duration, or number and duration of treatments. Immunosuppressant use was associated with a higher seroprevalence rate (63.4%) compared with no immunosuppressant use (55.9%; p=0.040). Conclusions: Canadian MS patients had an overall anti-JCV antibody seroprevalence that was consistent with previous studies using the two-step ELISA. Significant associations of anti-JCV antibody positivity were found with age, sex, region, and immunosuppressant therapy, whereas seroprevalence was not associated with race, MS type, MS duration, or number or duration of MS treatments.

Objective: To describe the social, clinical and use-patterns characteristics of medicinal marijuana use among patients with epilepsy (PWEs). Methods: Eighteen PWEs with prescriptions for medicinal marijuana from a Canadian adult-epilepsy clinic were included in this study. Results: Eighteen patients had a prescription of medicinal marijuana from a total population of 800 PWEs in our center (2.2%). Mean age of patients was 30±7.4 (19-50) years. Twelve (67%) patients were males. Eleven (61%) patients had drug-resistant epilepsy. Eleven (61%) patients suffered a psychiatric comorbidity and reported the use of illicit substances or heavy alcohol or tobacco consumption. Only two (11%) patients were married; the rest of patients (89%) were single or divorced. The drug use pattern was similar among patients. All patients asked for marijuana permission in the epilepsy clinic. Most (83%) had a previous history of marijuana smoking, with a mean of 6.6±3 (1-15) years. The mean consumption dose was 2.05±1.8 (0.5-8) grams per day. Ten (56%) patients reported withdrawal seizure exacerbation when they stopped the marijuana. Only two patients (11%) reported side effects, and all patients found medicinal marijuana very helpful for seizure control and improvement of mood disorder. Conclusions: PWEs using medicinal marijuana have a common profile. They are usually young single men with drug-resistant epilepsy and psychiatric comorbidity. Most used marijuana before formal prescription and all believe the drug was effective on their seizure control. Because of the concurrent use of other antiseizure medications, it is complex to estimate the actual effect of marijuana.

Background: A large hexanucleotide repeat expansion in C9orf72 has been identified as the most common genetic cause in familial amyotrophic lateral sclerosis and frontotemporal dementia. Rapid Eye Movement Sleep Behavior Disorder (RBD) is a sleep disorder that has been strongly linked to synuclein-mediated neurodegeneration. The aim of this study was to evaluate the role of the C9orf72 expansions in the pathogenesis of RBD. Methods: We amplified the C9orf72 repeat expansion in 344 patients with RBD by a repeat-primed polymerase chain reaction assay. Results: We identified two RBD patients carrying the C9orf72 repeat expansion. Most interestingly, these patients have the same C9orf72 associated-risk haplotype identified in 9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia families. Conclusions: Our study enlarges the phenotypic spectrum associated with the C9orf72 hexanucleotide repeat expansions and suggests that, although rare, this expansion may play a role in the pathogenesis of RBD.

Background: Patients with the postural instability and gait difficulty (PIGD) subtype of Parkinson disease (PD) are at a higher risk of dysfunction and are less responsive to dopamine replacement therapy. The PIGD subtype was found to largely associate with white matter lesions, but details of the diffusion changes within these lesions have not been fully investigated. Voxel-based analysis for diffusion tensor imaging data is one of the preferred measures to compare diffusion changes in each voxel in any part of the brain. Methods: PD patients with the PIGD (n=12) and non-PIGD subtypes (n=12) were recruited to compare diffusion differences in fractional anisotropy, axial diffusivity, and radial diffusivity with voxel-based analysis. Results: Significantly reduced fractional anisotropy in bilateral superior longitudinal fasciculus, bilateral anterior corona radiata, and the left genu of the corpus callosum were shown in the PIGD subtype compared with the non-PIGD subtype. Increased radial diffusivity in the left superior longitudinal fasciculus was found in the PIGD subtype with no statistical differences in axial diffusivity found. Conclusions: Our study confirms previous findings that white matter abnormalities were greater in the PIGD subtype than in the non-PIGD subtype. Additionally, our findings suggested: (1) compared with the non-PIGD subtype, loss of white matter integrity was greater in the PIGD subtype; (2) bilateral superior longitudinal fasciculus may play a critical role in microstructural white matter abnormalities in the PIGD subtype; and (3) reduced white matter integrity in the PIGD subtype could be mainly attributed to demyelination rather than axonal loss.

Silas Weir Mitchell (1829-1914), one of the fathers of American neurology, is well known for many contributions to neurology. However, his efforts in epilepsy are overshadowed by his other accomplishments. Mitchell introduced a new bromide preparation, lithium bromide, as a viable therapy. His most widely accepted contribution to the field was the introduction of inhaled amyl nitrite for early termination of seizures accompanied by an appropriate aura. Despite the prevalent views on lifestyle modification as a treatment for epilepsy during this time period, as well as Mitchell's own development of the “rest cure” for certain disease states, he was not a proponent of these types of interventions for epilepsy, nor did he support interventions focused on other organ systems, such as abdominal or gynecologic surgery. Mitchell had distinct opinions on the treatment of epilepsy, and helped to advance its therapeutics during his career.