After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease that targets motor neurons. Upper motor neurons degeneration is pathologically characterized by brain iron accumulation. Signal attenuation in the shape of a ribbon at the posterior border of the precentral gyrus can be observed on conventional magnetic resonance imaging (MRI) sequences including T2-weighted sequence. Methods: With the aim to know the qualities of this potential marker of ALS, we conducted a prospective study. Patients with definite ALS in the age range of 40–70 years and healthy controls underwent 3T brain MRI using a standardized sequence. A second MRI was performed 18 months later under the same conditions in the patients with ALS. Results: Most of the patients with ALS (91.66%) exhibited a “black ribbon” (BR) with an average area of 79.98 mm3. Signal attenuation discriminated ALS with a mean value of 63.97 arbitrary units (AU) on the left BR (95% CI: 60.67–67.27), a mean value of 59.15 AU (95% CI: 54.78–63.53) on the right BR, and a significant difference with control subjects presenting a mean value of 107.85 AU (p < 0.001). The optimal cut-off point for differentiating patients with ALS from controls (sensitivity, 0.92; specificity, 0.93) was 83 AU. Forced vital capacity and muscle strength in the contralateral upper extremity were significantly correlated with the ribbon intensity in ALS. Patients who underwent a second study exhibited significant changes in the BR related to the rapid evolution of the disease. Conclusions: This marker represents a valuable tool for the selection of candidates and their follow-up in clinical trials.

Recent therapeutic advances in the management of multiple sclerosis (MS) have raised questions about the selection of appropriate patient candidates for various treatments and, if the plan is to move from one treatment to another, the appropriate sequencing of these therapies. The selected approach should provide optimal disease management without limiting future therapeutic options based on safety concerns, and recognize potential future treatments and the possibility of combination therapies. Additional challenges include incorporation of patient needs and preferences into the overall therapeutic approach, in order to ensure optimal outcomes in the short and long term. The objective of this manuscript is to provide an overview of what is currently known regarding the impact of various therapies for MS on future therapeutic choices (sequencing). In this context, we reviewed the available evidence in support of various treatments and, based on the presence of disease activity, suggested a scheme for switching or escalating therapy with the main focus on sequencing of therapeutic approaches.

Background Survival estimates are integral to care for patients diagnosed with dementia. Few Canadian studies have carried out long-term follow-up of well-described cohorts, analyzing survival related to multiple risk factors. Methods Survival analysis of an inception cohort enrolled at a British Columbia (BC) tertiary dementia referral clinic between 1997 and 1999 was undertaken. Vital status was completed for 168 patients diagnosed with dementia. An evaluation of the effects of demographics, vascular risk factors, cognitive and functional ratings, apolipoprotein 4-status, and cholinesterase use on survival was performed using a log-rank test and time-dependent Cox regression. Survival of this dementia cohort was compared with the age-matched life expectancy of persons in BC. Results In all, 158/168 (94.0%) subjects died over 16.6 years, with a median survival of 7.08 years. Risk factors associated with shorter survival in dementia groups included age of onset ≥80 (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.05-2.32); greater functional disability (Disability Assessment for Dementia<55% [HR 1.47, 95% CI 1.04-2.08]); and cumulative medical illness severity (Cumulative Illness Rating Scale≥7 [HR 1.51, 95% CI 1.08-2.12)]. Compared with the BC population, years of potential life lost for dementia subjects aged <65 was 15.36 years, and for dementia subjects aged ≥80 it was 1.82 years. Conclusions Survival in dementia subjects is shorter than population life expectancies for each age strata, with greatest impact on younger patients. For people diagnosed with dementia, age ≥80 years, cumulative medical illness severity, and functional disabilities are the most significant survival predictors and can be used to guide prognosis.

Background: Neuromuscular disorders are a phenotypically and genotypically diverse group of diseases that can be difficult to diagnose accurately because of overlapping clinical features and nonspecific muscle pathology. Next-generation sequencing (NGS) is a high-throughput technology that can be used as a more time- and cost-effective tool for identifying molecular diagnoses for complex genetic conditions, such as neuromuscular disorders. Methods: One hundred and sixty-nine patients referred to a Canadian neuromuscular clinic for evaluation of possible muscle disease were screened with an NGS panel of muscular dystrophy–associated genes. Patients were categorized by the reason of referral (1) muscle weakness (n=135), (2) recurrent episodes of rhabdomyolysis (n=18), or (3) idiopathic hyperCKemia (n=16). Results: Pathogenic and likely pathogenic variants were identified in 36.09% of patients (61/169). The detection rate was 37.04% (50/135) in patients with muscle weakness, 33.33% (6/18) with rhabdomyolysis, and 31.25% (5/16) in those with idiopathic hyperCKemia. Conclusions: This study shows that NGS can be a useful tool in the molecular workup of patients seen in a neuromuscular clinic. Evaluating the utility of large panels of a muscle disease-specific NGS panel to investigate the genetic susceptibilities of rhabdomyolysis and/or idiopathic hyperCKemia is a relatively new field. Twenty-eight of the pathogenic and likely pathogenic variants reported here are novel and have not previously been associated with disease.

Background: Neurolymphomatosis is a process of neoplastic endoneurial invasion, most strongly associated with non-Hodgkin’s lymphoma. It must be distinguished from paraneoplastic, metabolic, nutritional and treatment-related causes of neuropathy that are common in this patient population. Methods: This brief case series illustrates the protean manifestations of neurolymphomatosis of the brachial plexus, ranging from focal distal mononeuropathy to multifocal brachial plexopathy, either as the index manifestation of lymphoma or as a complication of relapsing disease. Results: Prominent asymmetry, pain and nodular involvement on neuroimaging may help distinguish neurolymphomatosis from paraneoplastic immune demyelinating radiculoneuropathy. MR neurography criteria for the diagnosis of neurolymphomatosis include hyperintensity on T2 and STIR sequences, focal and diffuse nerve enlargement with fascicular disorganization and gadolinium enhancement. No specific anatomical distribution within the brachial plexus has, however, been found to be characteristic. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is the imaging modality with the highest sensitivity for detection of nodal or extranodal spread in lymphoma. Conclusions: Brachial plexus neuropathy in neurolymphomatosis is highly protean in its distribution, semiology and relation to lymphoma staging. Dedicated MRI and PET-CT imaging are leading diagnostic modalities.

Background: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. Methods: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. Results: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. Conclusions: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-β2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-β1, TBR-II, homocysteine, and interleukins (particularly IL-1β, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aβ42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

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.

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.

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.

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.

Background: The timing of the circulatory determination of death for organ donation presents a medical and ethical challenge. Concerns have been raised about the timing of electrocerebral inactivity in relation to the cessation of circulatory function in organ donation after cardio-circulatory death. Nonprocessed electroencephalographic (EEG) measures have not been characterized and may provide insight into neurological function during this process. Methods: We assessed electrocortical data in relation to cardiac function after withdrawal of life-sustaining therapy and in the postmortem period after cardiac arrest for four patients in a Canadian intensive care unit. Subhairline EEG and cardio-circulatory monitoring including electrocardiogram, arterial blood pressure (ABP), and oxygen saturation were captured. Results: Electrocerebral inactivity preceded the cessation of the cardiac rhythm and ABP in three patients. In one patient, single delta wave bursts persisted following the cessation of both the cardiac rhythm and ABP. There was a significant difference in EEG amplitude between the 30-minute period before and the 5-minute period following ABP cessation for the group, but we did not observe any well-defined EEG states following the early cardiac arrest period. Conclusions: In a case series of four patients, EEG inactivity preceded electrocardiogram and ABP inactivity during the dying process in three patients. Further study of the electroencephalogram during the withdrawal of life sustaining therapies will add clarity to medical, ethical, and legal concerns for donation after circulatory determined death.

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: Interhospital transfer is an important but resource-intensive pattern of care. The use for stroke patients is highly dependent upon health system structure. We examined the impact of hospital transfers for stroke care in Canada. Methods: We analyzed hospital administrative data within the Canadian Institute for Health Information (CIHI) Database for the 3 fiscal years 2011/12, 2012/13 and 2013/14. Patients with clinical stroke syndrome (ischemic or hemorrhagic) were identified using International Classification of Diseases. Stroke centers were defined by Heart & Stroke Foundation of Canada stroke report. Results: During the 3-year period,397 patients in Canada (excluding Quebec) were admitted to hospital for clinical stroke syndrome. Median age was 75 (interquartile range [IQR] 64–84) years; 50.6 % were male. Less than 5% (n=4030) of patients were transferred. Patients transferred to stroke centers were younger (p<0.001) and had shorter median length of stay (p<0.001). The highest probability of discharge home was associated with sole care at stroke center (43.8%). Transfer to stroke center from community hospital had the highest probability for discharge to rehabilitation facility (25%) and lowest to either long-term (2.1%) or complex community care (2.0%). Transferred patients had lower mortality at discharge. Conclusion: Younger patients were transferred more frequently to stroke centers; older patients were more likely treated in community hospitals. Sole stroke center care was associated with high discharge rate to home; transfer to a stroke center was associated with high discharge rate to rehabilitation and lower mortality rates.

Abnormal fetal corticogenesis results in malformations of cortical development (MCD). Abnormal cell proliferation leads to microcephaly or megalencephaly, incomplete neuronal migration results in heterotopia and lissencephaly, neuronal overmigration manifests as cobblestone malformations, and anomalous postmigrational cortical organization is responsible for polymicrogyria and focal cortical dysplasias. MCD comprises various congenital brain disorders, caused by different genetic, infectious, or vascular etiologies and is associated with significant neurological morbidity. Although MCD are rarely diagnosed prenatally, both dedicated multiplanar neurosonography and magnetic resonance imaging enable good demonstration of fetal cortical development. The imaging signs of fetal MCD are: delayed or absent cerebral sulcation; premature abnormal sulci; thin and irregular hemispheric parenchyma; wide abnormal overdeveloped gyri; wide opening of isolated sulci; nodular bulging into the lateral ventricles; cortical clefts; intraparenchymal echogenic nodules; and cortical thickening. The postnatal and prenatal imaging features of four main malformations of cortical development—lissencephaly, cobblestone malformations, periventricular nodular heterotopia, and polymicrogyria—are described.

Positron emission tomography (PET) imaging of brain amyloid beta is nowclinically available in several countries including the United States andthe United Kingdom, but not Canada. It has become an established techniquein the field of neuroimaging of aging and dementia, with data incorporatedin the new consensus guidelines for the diagnosis of Alzheimer disease andpredementia Alzheimer’s disease–related conditions. At this point, there arethree US Food and Drug Administration– and European Union–approved tracers.Guided by appropriate use criteria developed in 2013 by the Alzheimer’sAssociation and the Society of Nuclear Medicine and Molecular Imaging, theutility of amyloid imaging in medical practice is now supported by a growingbody of research. In this paper, we aimed to provide an update on the 2012Canadian consensus guidelines to dementia care practitioners on proper useof amyloid imaging. We also wished to generate momentum for the industry tosubmit a new drug proposal to Health Canada. A group of local, national, andinternational dementia experts and imaging specialists met to discussscenarios in which amyloid PET could be used appropriately. Peer-reviewedand published literature between January 2004 and May 2015 was searched.Technical and regulatory considerations pertaining to Canada wereconsidered. The results of a survey of current practices in Canadiandementia centers were considered. A set of specific clinical and researchguidelines was agreed on that defines the types of patients and clinicalcircumstances in which amyloid PET could be used in Canada. Future researchdirections were also outlined, notably the importance of studies that wouldassess the pharmaco-economics of amyloid imaging.

Background: Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non–evidence-based medical tourism for CCSVI procedures. Methods: We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. Results: In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. Conclusions: Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized.

Background: The Canadian Neurological Society commissioned a manpower survey in 2012 to assess Canadian neurological manpower and resources.Methods: Surveys were sent electronically to all Canadian neurologists with available email addresses. Responses were analysed for effects of physician gender, age, geographic location (eastern or western Canada) or type of practice (academic, community). Questions focused on work patterns, neurologic conditions treated, access to or performance of procedures, and service and manpower issues.Results: A total of 694 of 854 neurologists in Canada were surveyed and 219 (32%) responded. Respondents were 70% male with mean age of 50 years. Neurologists worked an average of 57 hours/week and saw a mean of 40 patients per week. There were significant differences in number of patients seen, types of practice, and areas of neurological specialization between community and academic neurologists. Fifty percent of neurologists report shortages of neurologists in their community, particularly of general adult neurologists. Wait times for neurological services exceeded international standards for consultations and also were longer than Canadian averages for other specialists. More community (18%) than academic (5%) neurologists planned to retire within the next 5 years.Conclusions: The demand for neurological services continues to outstrip resources despite the increased number of neurologists. Impending retirement of community neurologists will exacerbate manpower issues unless adequate numbers of trainees choose general neurologic practice in the community as a career.