Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.

In this review, the available evidence to guide clinicians regarding eligibility for deep brain stimulation (DBS) in the main conditions in which these forms of therapy are generally indicated—Parkinson’s disease (PD), tremor, and dystonia—is presented. In general, the literature shows that DBS is effective for PD, essential tremor, and idiopathic dystonia. In these cases, key points in patient selection must include the level of disability and inability to manage symptoms using the best available medical therapy. Results are, however, still not optimal when dealing with other aetiologies, such as secondary tremors and symptomatic dystonia. Also, in PD, issues such as age and neuropsychiatric profile are still debatable parameters. Overall, currently available literature is able to guide physicians on basic aspects of patient selection and indications for DBS; however, a few points are still debatable and controversial. These issues should be refined and clarified in future studies.

Pompe disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratory weakness with or without cardiomyopathy. The objective of our review was to systematically evaluate the quality of evidence from the literature to formulate evidence-based guidelines for the diagnosis and management of patients with Pompe disease. The literature review was conducted using published literature, clinical trials, cohort studies and systematic reviews. Cardinal treatment decisions produced seven management guidelines and were assigned a GRADE classification based on the quality of evidence in the published literature. In addition, six recommendations were made based on best clinical practices but with insufficient data to form a guideline. Studying outcomes in rare diseases is challenging due to the small number of patients, but this is in particular the reason why we believe that informed treatment decisions need to consider the quality of the evidence.

Recently, many cases of autoimmune limbic encephalitis with positive GAD65 (glutamic acid decarboxylase) antibodies have been described in the scientific literature. However, it remains an understudied topic of great relevance to practicing neurologists. Thus, we report here a review of published cases, in English, of autoimmune limbic encephalitis with this type of antibodies, focusing on presenting symptoms and signs, associated conditions, and findings upon investigation. We also report treatment responses. We aim to offer a better description of the clinical spectrum of autoimmune limbic encephalitis associated with GAD65 antibodies as well as to expose its paraclinical features and outcome.

Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM.

Positron emission tomography (PET) imaging of brain amyloid beta is now clinically available in several countries including the United States and the United Kingdom, but not Canada. It has become an established technique in the field of neuroimaging of aging and dementia, with data incorporated in the new consensus guidelines for the diagnosis of Alzheimer disease and predementia Alzheimer’s disease–related conditions. At this point, there are three US Food and Drug Administration– and European Union–approved tracers. Guided by appropriate use criteria developed in 2013 by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, the utility of amyloid imaging in medical practice is now supported by a growing body of research. In this paper, we aimed to provide an update on the 2012 Canadian consensus guidelines to dementia care practitioners on proper use of amyloid imaging. We also wished to generate momentum for the industry to submit a new drug proposal to Health Canada. A group of local, national, and international dementia experts and imaging specialists met to discuss scenarios in which amyloid PET could be used appropriately. Peer-reviewed and published literature between January 2004 and May 2015 was searched. Technical and regulatory considerations pertaining to Canada were considered. The results of a survey of current practices in Canadian dementia centers were considered. A set of specific clinical and research guidelines was agreed on that defines the types of patients and clinical circumstances in which amyloid PET could be used in Canada. Future research directions were also outlined, notably the importance of studies that would assess the pharmaco-economics of amyloid imaging.

Objective: The Montreal Cognitive Assessment (MoCA) is a general cognitive screening tool that has shown sensitivity in detecting mild levels of cognitive impairment in various clinical populations. Although mood dysfunction is common in referrals to memory clinics, the influence of mood on the MoCA has to date been largely unexplored. Method: In this study, we examined the impact of mood dysfunction on the MoCA using a memory clinic sample of individuals with depressive symptoms who did not meet criteria for a neurodegenerative disease. Results: Half of the group with depressive symptoms scored below the MoCA-suggested cutoff for cognitive impairment. As a group, they scored below healthy controls, but above individuals with Alzheimer’s disease and frontotemporal dementia. A MoCA subtask analysis revealed a pattern of executive/attentional dysfunction in those with depressive symptoms. Conclusions: This observed negative impact of depressive symptomatology on the MoCA has interpretative implications for its utility as a cognitive screening tool in a memory clinic setting.

Objective: To study the relationship of Nε-(carboxymethyl)-lysine level (CML) with microstructure changes of white matter (WM), and cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and to discuss the potential mechanism underlying T2DM-associated cognitive impairment. Methods: The study was performed in T2DM patients (n=22) with disease course ≥5 years and age ranging from 65 to 75 years old. A control group consisted of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML levels were measured by enzyme-linked immunosorbent assay, and cognitive function was assessed by Mini-Mental State Examination and Montreal cognitive assessment (MoCA). Results: The total Mini-Mental State Examination score in the patient group (25.72±3.13) was significantly lower than the control group (28.16±2.45) (p<0.05). In addition, the total MoCA score in the patient group (22.15±3.56) was significantly lower than the control group 25.63±4.12) (p<0.01). In the patient group, FA values were significantly decreased in the corpus callosum, cingulate fasciculus, inferior fronto-occipital fasciculus, parietal WM, hippocampus, and temporal lobes relative to corresponding regions of healthy controls (p<0.05). Plasma CML level was negatively correlated with average FA values in the global brain (r=−0.58, p<0.01) and MoCA scores (r=−0.47, p<0.05). Conclusions: In T2DM, WM microstructure changes occur in older patients, and elevations in CML may play a role in the development of cognitive impairment.

Background: Transient ischemic attack (TIA) and minor stroke are associated with a substantial risk of subsequent stroke; however, there is uncertainty about whether such patients require admission to hospital for their initial management. We used data from a clinical stroke registry to determine the frequency and predictors of hospitalization for TIA or minor stroke across the province of Ontario, Canada. Methods: The Ontario Stroke Registry collects information on a population-based sample of all patients seen in the emergency department with acute stroke or TIA in Ontario. We identified patients with minor ischemic stroke or TIA included in the registry between April 1, 2008, and March 31, 2011, and used multivariable analyses to evaluate predictors of hospitalization. Results: Our study sample included 8540 patients with minor ischemic stroke or TIA, 47.2% of whom were admitted to hospital, with a range of 37.6% to 70.3% across Ontario’s 14 local health integration network regions. Key predictors of admission were preadmission disability, vascular risk factors, presentation with weakness, speech disturbance or prolonged/persistent symptoms, arrival by ambulance, and presentation on a weekend or during periods of emergency department overcrowding. Conclusions: More than one-half of patients with minor stroke or TIA were not admitted to the hospital, and there were wide regional variations in admission patterns. Additional work is needed to provide guidance to health care workers around when to admit such patients and to determine whether discharged patients are receiving appropriate follow-up care.

Background: Image review on computer-based workstations has made film-based review outdated. Despite advances in technology, the lack of portability of digital workstations creates an inherent disadvantage. As such, we sought to determine if the quality of image review on a handheld device is adequate for routine clinical use. Methods: Six CT/CTA cases and six MR/MRA cases were independently reviewed by three neuroradiologists in varying environments: high and low ambient light using a handheld device and on a traditional imaging workstation in ideal conditions. On first review (using a handheld device in high ambient light), a preliminary diagnosis for each case was made. Upon changes in review conditions, neuroradiologists were asked if any additional features were seen that changed their initial diagnoses. Reviewers were also asked to comment on overall clinical quality and if the handheld display was of acceptable quality for image review. Results: After the initial CT review in high ambient light, additional findings were reported in 2 of 18 instances on subsequent reviews. Similarly, additional findings were identified in 4 of 18 instances after the initial MR review in high ambient lighting. Only one of these six additional findings contributed to the diagnosis made on the initial preliminary review. Conclusions: Use of a handheld device for image review is of adequate diagnostic quality based on image contrast, sharpness of structures, visible artefacts and overall display quality. Although reviewers were comfortable with using this technology, a handheld device with a larger screen may be diagnostically superior.

Introduction: Impaired collateral circulation can lead to stroke during carotid endarterectomy. Carotid stump pressure (CSP) is used as a surrogate measure of collateral flow. The objective was to determine whether anatomical features obtained from digital subtraction angiography correlate with CSP during temporary internal carotid artery occlusion. The second objective was to use these features in combination to predict CSP. Methods: Digital subtraction angiographies from 102 patients obtained before endarterectomy were reviewed for anatomical variables including: degree of ipsilateral and contralateral carotid artery stenosis; patency of the anterior communicating artery; presence of cross-flow into ipsilateral middle cerebral artery branches; and size (< or ≥1 mm calibre) of the ipsilateral proximal anterior cerebral (A1), the contralateral A1, and the ipsilateral posterior communicating arteries. At surgery, systemic mean arterial pressure (MAP) and CSP were recorded. Multiple regression analysis was used to assess for anatomical features significantly associated with CSP. A “predicted CSP” equation was applied to 54 subsequent patients and correlated with measured CSP. Results: Variables correlating with CSP included MAP (p=0.001); the presence of severe contralateral carotid stenosis (p=0.002); patency of the anterior communicating artery (p=0.013); and the size of the contralateral A1 segment (p=0.029). Angiographic cross-flow, ipsilateral A1 size, and ipsilateral posterior communicating artery size were not significant. Predicted CSP correlated significantly with measured CSP (p<0.0001; R2=0.34). Conclusions: Anatomical features and systemic MAP are associated with carotid stump pressure during internal carotid artery occlusion and account for a significant amount of its variation.

Introduction: The Circle of Willis (CoW) is the most effective collateral circulation to the brain during internal carotid artery (ICA) occlusion. Carotid stump pressure (CSP) is an established surrogate measure of the cerebral collateral circulation. This study aims to use hemodynamic and computed tomography angiography measurements to determine the strongest influences upon the dependent variable, CSP. These findings could help clinicians noninvasively assess the adequacy of the collateral circulation and facilitate surgical risk assessment in an outpatient setting. Methods: CSP and mean arterial pressure were measured during carotid endarterectomy or during carotid balloon test occlusion in 92 patients. Intracranial arterial diameters were measured on computed tomography angiography at 16 different locations. Univariate and multivariate analyses were used to determine the key factors associated with CSP. In a subgroup of individuals (n=27) with severe (>70% North American Symptomatic Carotid Endarterectomy Trial) contralateral stenosis or occlusion, the same analysis was performed. Results: The contralateral anterior cerebral artery proximal to anterior communicating artery (A1) of the CoW had the strongest influence upon CSP, followed by the mean arterial pressure, the contralateral ICA diameter, and the anterior communicating artery diameter (R2=0.364). In the subgroup with high-grade contralateral ICA stenosis, the ipsilateral posterior communicating artery exerted the strongest influence (R2=0.620). Conclusions: During ICA occlusion, the anterior CoW dominates in preserving collateral flow, especially the contralateral A1 segment. In individuals with high-grade contralateral carotid stenosis, the posterior communicating artery calibre becomes a dominant influence. The most favourable anatomy consists of large contralateral A1 and anterior communicating arteries, and no contralateral carotid stenosis.

Background: The acquisition of a new 320-row multidetector computed tomography angiography (CTA) scanner at the Montreal Neurological Institute and Hospital has provided higher quality imaging with less radiation exposure and shorter time of acquisition. However, its reliability has not been fully proven in critical vascular lesions when it comes to replacing a more invasive examination such as cerebral angiography. We wished to validate the accuracy of this equipment to investigate four common indications for patients to undergo conventional digital subtraction angiography: subarachnoid hemorrhage, vasospasm, unusual intracerebral hemorrhage, and unruptured aneurysm. Methods: Radiological reports and relevant imaging from 82 consecutive subjects who underwent a 320-row multidetector CTA followed by cerebral angiography from February 2010 to February 2014 were retrospectively analysed. A total of 102 cerebrovascular anomalies were found. Reports from both imaging modalities were compared to determine the diagnostic accuracy of CTA. Results: The overall sensitivity and specificity of 320-row multidetector CTA for detecting cerebrovascular abnormalities were, respectively, 97.60% and 63.20%. Similar results were obtained for all four categories of clinical indications. Conclusion: Results obtained from CTA were consistent with those obtained on digital subtraction angiography regardless of the vascular pathology. To our knowledge, this study is the first validating the accuracy of 320-row CTA in diagnosing critical cerebrovascular lesions.

Background: Pediatric neurology trainee numbers have grown considerably in Canada; recent research, however, has shown that the number of pediatric neurology graduates is outpacing the need for future pediatric neurologists. The purpose of this study was to seek the opinion of pediatric neurology program directors and trainees regarding possible solutions for this issue. Methods: Two focus groups were convened during the Canadian Neurological Sciences Federation annual congress in June 2012; one consisted of current and former program directors, and the other of current pediatric neurology trainees. Groups were asked for their perceptions regarding child neurology manpower issues in Canada as well as possible solutions. Focus groups were audio-recorded and transcribed for analysis. Theme-based qualitative analysis was used to analyze the transcripts. Results: Major themes emerging from both focus groups included the emphasis on community pediatric neurology as a viable option for trainees, including the need for community mentors; recognizing the needs of underserviced areas; and establishing academic positions for community preceptors. The need for career mentoring and support structures during residency training was another major theme which arose. Program directors and trainees also gave examples of ways to reduce the current oversupply of trainees in Canada, including limiting the number of trainees entering programs, as well as creating a long-term vision of child neurology in Canada. Conclusions: A nationwide dialogue to discuss the supply and demand of manpower in academic and community pediatric neurology is essential. Career guidance options for pediatric neurology trainees across the country merit further strengthening.

Background: In response to the rising incidence of concussions among children and adolescents, the province of Ontario recently introduced the Ontario Policy/Program Memorandum on Concussions (PPM No. 158) requiring school boards to develop a concussion protocol. As this is the first policy of its kind in Canada, the impact of the PPM is not yet known. Methods: An electronic survey was sent to all high school principals in the Toronto District School Board 1 year after announcement of the PPM. Questions covered extent of student, parent, and staff concussion education along with concussion management protocols. Results: Of 109 high school principals contacted, 39 responded (36%). Almost all schools provided concussion education to students (92%), with most education delivered through physical education classes. Nearly all schools had return to play (92%) and return to learn (77%) protocols. Although 85% of schools educated staff on concussions, training was aimed at individuals involved in sports/physical education. Only 43.6% of schools delivered concussion education to parents, and many principals requested additional resources in this area. Conclusions: One year after announcement of the PPM, high schools in the Toronto District School Board implemented significant student concussion education programs and management protocols. Staff training and parent education required further development. A series of recommendations are provided to aid in future concussion policy development.

Background: Previous reports suggest that although a diagnostic muscle biopsy can confirm the presence of Pompe disease, the absence of a definitive biopsy result does not rule out the diagnosis. Methods: In this study, we reviewed patients with a limb-girdle syndrome who demonstrated nonspecific abnormalities of muscle, without evidence of the classical changes of acid maltase deficiency. These patients were rescreened for Pompe disease using dried blood spot (DBS) testing. Results: Twenty-seven patients provided blood samples for the DBS test. Four patients underwent subsequent genetic testing. Genetic analysis demonstrated that one patient tested positive for Pompe disease and one patient had one copy of a pathogenic variant. Conclusions: In conclusion, the ability of a diagnostic muscle biopsy to definitively rule out the presence of Pompe disease is limited. There is a role for a screening DBS in all patients presenting with a limb-girdle syndrome without a clear diagnosis.

Background: Patients with Rett syndrome (RTT) may demonstrate parkinsonian features. Here, we report a preliminary cross-sectional and prospective evaluation of the evolution, regional distribution, and eventual incidence of rigid tone in a cohort of MECP2 mutation-positive patients. Methods: In 51 participants, muscle tone rigidity in extremity regions and neck plus hypomimia were quantified using an RTT rigidity distribution (RTTRD) score with a range of 0 to 15. RTTRD scores were correlated with age, ability to walk and speak, mutation type, and, in a small subgroup (n=9), cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid levels. Results: Participant ages ranged from 2 years and 5 months, to 54 years. Rigidity was found in 43/51 (84.3%); it appeared as early as age 3, increased in extent with age, and was present in all participants aged ≥13. Ankle region rigidity appeared first, followed by proximal legs, arms, neck, and face. Ambulatory participants (n=21) had lower RTTRD scores than nonambulatory (n=30; p=0.003). We found a trend to lower scores in participants with retained speech (n=13) versus those with none (n=38; p=0.074), and no difference in scores for those with truncating (n=25) versus missense mutations (n=22; p=0.387). RTTRD scores correlated negatively with CSF HVA levels (R=−0.83; p=0.005), but not with 5-hydroxyindole-acetic acid levels (R=−0.45; p=0.22). Conclusions: Although assessment of muscle tone is somewhat subjective and the RTTRD has not been validated, this study nevertheless suggests that parkinsonian rigidity in RTT is common and frequently increases in extent with age; its severity correlates directly with impaired ambulation and inversely with CSF HVA levels.