The current literature on the role of brain microbleeds (MB) on the neuropsychological outcomes of Alzheimer’s disease (AD) is heterogeneous. We therefore meta-analytically examined the neuropsychological literature pertaining to MBs in AD. Using a priori selected criteria, studies with cross-sectional neuropsychological assessment on MBs and AD were reviewed. Six of 122 studies met selection criteria and provided neuropsychological data on either AD with MB and without MB, or in contrast to healthy controls. The global neuropsychological difference between AD with MB and AD without MB based on random effect model was nonsignificant, heterogeneous, and small (Effect Size =−0.155; 95% confidence interval =−0.465 to 0.155; p value =0.326; Heterogenity: Q-value =12.744; degrees of freedom =5; p =0.026; I2 =61%). The contribution of MBs to cognitive deficits in AD remains unclear. Future studies of MB in AD should strive to use standardized neuroimaging techniques with high sensitivity for MB, a common standard for MB definition, and neuropsychological tests sensitive for detecting subtle cognitive impairment.

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.

Objective: Administrative data validation is essential for identifying biases and misclassification in research. The objective of this study was to determine the accuracy of diagnostic codes for acute stroke and transient ischemic attack (TIA) using the Ontario Stroke Registry (OSR) as the reference standard. Methods: We identified stroke and TIA events in inpatient and emergency department (ED) administrative data from eight regional stroke centres in Ontario, Canada, from April of 2006 through March of 2008 using ICD–10–CA codes for subarachnoid haemorrhage (I60, excluding I60.8), intracerebral haemorrhage (I61), ischemic (H34.1 and I63, excluding I63.6), unable to determine stroke (I64), and TIA (H34.0 and G45, excluding G45.4). We linked administrative data to the Ontario Stroke Registry and calculated sensitivity and positive predictive value (PPV). Results:: We identified 5,270 inpatient and 4,411 ED events from the administrative data. Inpatient administrative data had an overall sensitivity of 82.2% (95% confidence interval [CI95%]=81.0, 83.3) and a PPV of 68.8% (CI95%=67.5, 70.0) for the diagnosis of stroke, with notable differences observed by stroke type. Sensitivity for ischemic stroke increased from 66.5 to 79.6% with inclusion of I64. The sensitivity and PPV of ED administrative data for diagnosis of stroke were 56.8% (CI95%=54.8, 58.7) and 59.1% (CI95%=57.1, 61.1), respectively. For all stroke types, accuracy was greater in the inpatient data than in the ED data. Conclusion: The accuracy of stroke identification based on administrative data from stroke centres may be improved by including I64 in ischemic stroke type, and by considering only inpatient data.

Background: Understanding the epidemiology of traumatic brain injury (TBI) is essential to shape public health policy, implement prevention strategies, and justify allocation of resources toward research, education, and rehabilitation in TBI. There is not, to our knowledge, a systematic review of population-based studies addressing the epidemiology of TBI that includes all subtypes. We performed a comprehensive systematic review and meta-analysis of the worldwide incidence of TBI. Methods: A search was conducted on May 23, 2014, in Medline and EMBASE according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Abstracts were screened independently and in duplicate to identify original research. Study quality and ascertainment bias were assessed in duplicate using a previously published tool. Demographic data and incidence estimates from each study were recorded, along with stratification by age, gender, year of data collection, and severity. Results: The search strategy yielded 4944 citations. Two hundred and sixteen articles met criteria for full-text review; 144 were excluded. Hand searching resulted in ten additional articles. Eighty-two studies met all eligibility criteria. The pooled annual incidence proportion for all ages was 295 per 100,000 (95% confidence interval: 274-317). The pooled incidence rate for all ages was 349 (95% confidence interval: 96.2-1266) per 100,000 person-years. Incidence proportion and incidence rate were examined to see if associated with age, sex, country, or severity. Conclusions: We conclude that most TBIs are mild and most TBIs occur in males among the adult population. The incidence of TBI varies widely by ages and between countries. Despite being an important medical, economic, and social problem, the global epidemiology of TBI is still not well-characterized in the current literature. Understanding the incidence of TBI, particularly mild TBI, remains challenging because of nonstandardized reporting among neuroepidemiological studies.

Objective: The phrenic nerve and the contralateral seventh cervical (C7) nerve root are the most commonly used donor nerves in the treatment of total brachial plexus avulsion. The aim of this study was to determine if the phrenic nerve or the contralateral C7 nerve root yields a superior outcome for nerve transfer. Methods: A total of 60 Sprague-Dawley rats were randomly assigned to 1 of 3 groups. In Group A the phrenic nerve was used as the donor nerve; in Group B the contralateral C7 nerve root nerve was used as the donor nerve; in Group C the nerve was directly sutured. The results of behavioral assessment, electrophysiology, histology, nerve fiber count and muscle weight at 24 weeks postoperatively were recorded. Results: Group A showed a faster recovery time compared to Group B; however Group B showed a better functional recovery at the final outcome assessment compared to Group A. Conclusion: The contralateral C7 nerve root was better as the donor nerve for nerve transfer in the treatment of total brachial plexus avulsion.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative neurological disease with significant effects on quality of life. International studies continue to provide consistent incidence values, though complete case ascertainment remains a challenge. The Canadian population has been understudied, and there are currently no quantitative data on the incidence of ALS in British Columbia (BC). The objectives of this study were to determine the five-year incidence rates of ALS in BC and to characterize the demographic patterns of the disease. Methods: The capture–recapture method was employed to estimate ALS incidence over a five-year period (2010-2015). Two sources were used to identify ALS cases: one database from an ALS medical centre and another from a not-for-profit ALS organization. Results: During this time period, there were 690 incident cases within the two sources. The capture–recapture method estimated 57 unobserved cases, corresponding to a crude five-year incidence rate of 3.29 cases per 100,000 (CI95%=3.05-3.53). The mean age of diagnosis was 64.6 (CI95%=59.7-69.4), with 63.5 (CI95%=56.9-70.1) for men and 65.7 (CI95%=58.6-72.7) for women. There was a slight male preponderance in incidence, with a 1.05:1 ratio to females. Peak numbers in incidence occurred between the ages of 70 and 79. Conclusions: The incidence of ALS in BC was found to be consistent with international findings though nominally higher than that in other Canadian provinces to date.

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing degenerative motor neuron disease that results in significant muscle weakness. Defects in energy metabolism and difficulties in swallowing eventually lead to a reduction in body mass. Weight loss exacerbates symptoms and serves as an independent negative prognostic factor. Percutaneous endoscopic gastrostomy (PEG) is often inserted in patients with ALS to either supplement or replace oral feeding. However, the criteria for PEG placement and timing of insertion are important clinical decisions that have not been fully studied. Given the absence of guiding evidence, the aim of this project was to better understand how Canadian ALS clinics make decisions regarding gastrostomy feeding. Methods: ALS clinical directors across Canada were asked if they had written guidelines for timing of PEG insertion and if not, what criteria they use to make this decision. Responses from 10 of 17 centres contacted were received. Results: The approach to supplemental nutrition management in Canadian clinics varies in the absence of formal guidelines. Only one centre has a written set of centre-specific protocols in place. Most clinics considered some combination of respiratory decline, weight loss, dysphagia and/or patient readiness when reaching a decision. However, the absolute threshold and mechanism of measuring the individual criteria differed between clinics. Conclusions: Practices generally reflect international published recommendations but vary on the emphasis of specific criteria. Further research is required to determine the optimal timing and criteria to place gastrostomy feeding tubes in the ALS population.

Background: Hereditary hemochromatosis (HH) is a genetic disorder causing pathological iron deposition and functional impairment of various organs, predominantly the liver. We assessed patients with HH for the presence of movement disorders. Methods: We reviewed the charts of 616 patients with HH who attended hemochromatosis clinic at London Health Sciences Centre, London, ON, Canada, from 1988 to 2015. Results: We found three HH patients with movement disorders, without any other major systemic manifestation. One had parkinsonism, another had chorea, and the third had tremor. All three patients had evidence of iron deposition in the brain, affecting the basal ganglia in the first two, and the dentate nucleus, red nucleus, and substantia nigra in the third patient. In addition to the C282Y homozygous mutation in the HFE gene, two of our patients had non-HFE gene mutations. Conclusion: HH should be considered in the differential diagnosis of movement disorders with pathological brain iron deposition. We report for the first time chorea in a patient with HH. Non-HFE gene mutations may predispose HH patients to iron deposition in the brain.

Background: The prevalence of sleep disturbances among patients with Parkinson’s disease (PD) is estimated to occur in 37% to 98% of patients. Sleep disturbances have been associated with a reduced quality of life for patients with PD. The objective of this study was to assess the impact of rasagiline treatment on the severity of sleep disturbances among patients with idiopathic PD. Methods: In this open-label, multicentre study, 110 adult patients with idiopathic PD were treated with rasagiline either as monotherapy or as adjunct therapy. The primary endpoint was the change in severity of sleep disturbances, assessed with the PD Sleep Scale from baseline to month 2. Exploratory endpoints included change in daytime sleepiness, assessed with the Epworth Sleep Scale, treatment satisfaction measured with the Treatment Satisfaction Questionnaire for Medication, patient’s overall improvement or deterioration over time measured with the Clinical Global Impression of Improvement, tolerability, and safety. Findings: Patients treated with rasagiline as mono- or adjunct therapy showed a statistically significant improvement in sleep quality after 2 months. There was no change in daytime sleepiness. Overall, patients were satisfied with rasagiline treatment with a mean Treatment Satisfaction Questionnaire for Medication [standard deviation] total score at month 2 of 68% [16.1]. At the end of study, 64 patients (65.9%) were judged, by the investigator, as being at least minimally improved from baseline on the Clinical Global Impression of Improvement. Rasagiline was safe and well-tolerated. Interpretation: Rasagiline as mono- or adjunct-therapy may improve sleep experience in patients with PD in the short term.

Background: Anticholinergic and sedating medications are generally contraindicated in those with cognitive decline. We examined trends in medication use by patients at initial presentation to a rural and remote memory clinic (RRMC) between March 2004 and June 2015 to determine whether patterns of medication use have changed. Methods: The first 444 patients seen at the RRMC between 2004 and 2015 were included in this analysis. Medication lists were collected at the patient’s initial visit, and it was noted whether patients were taking anticholinergic or potentially sedating drugs. Statistical analysis (Spearman’s correlation) was conducted to examine trends in medication use over time. Results: Patients were on a mean of 5.18 medications (standard deviation, 3.46). Ninety-one patients (20.5%) were taking at least one anticholinergic medication. There was a decline (25.0% in 2004 to 12.5% in 2014) in percentage of patients presenting with anticholinergic medications over the 11 years of this study (Spearman’s correlation coefficient =−0.64, p=0.035). The prevalence of drugs acting on the central nervous system trended toward an increase, but this was not statistically significant. Sixty-three patients (14.2%) presented to the RRMC already taking a cholinesterase inhibitor. Conclusions: The most encouraging statistic to come from this study is a decline in anticholinergic medication use in this rural population. Prescribers must be properly informed to ensure that the number of medications per patient does not continue to rise, that medications are used only as necessary, and that potentially deleterious medications are avoided.

Background: An increased incidence of hospital admissions coded as acute disseminated encephalomyelitis (ADEM) was noted in Winnipeg, Manitoba, Canada, during the second wave of the influenza pandemic from October 2009 to March 2010. However, it was not clear whether this was due to heightened awareness of potential neurological complications of influenza or influenza vaccination or an actual increase in the number of cases. Methods: We extracted data from the charts of 139 patients hospitalized with an International Classification of Diseases-10 discharge code indicating ADEM (G04.0) or unspecified noninfectious encephalitis or myelitis (G04.8, G04.9) between January 2006 and December 2012. Clinical and laboratory data were reviewed by a neurologist, and diagnoses were determined using the Brighton criteria. Results: Over the entire study period, there were 22 cases of ADEM. During the peak pandemic period (April-December 2009), seven patients were hospitalized with ADEM, corresponding to a rate of 7.8/million/year; 4.7 (95% confidence interval: 1.9-11.4) times higher than the rate before or after the pandemic period. Only one patient with ADEM had received the monovalent A(H1N1)pdm09 vaccine within 12 weeks of hospitalization. Conclusions: We have found an increased incidence of ADEM during the pandemic period that may be related, at least in part, to the increased incidence of influenza during that period. However, there was no temporal relationship with the administration of A(H1N1)pdm09 or seasonal influenza vaccines. Our study provides reassurance that use of these vaccines was not associated with increased risk of ADEM.

Background: Chronic ataxia, greater than two months in duration, is encountered relatively commonly in clinical pediatric neurology practise and presents with diagnostic challenges. It is caused by multiple and diverse disorders. Our aims were to describe the neuroimaging features and the value of repeat neuroimaging in pediatric chronic ataxia to ascertain their contribution to the diagnosis and management. Materials and Methods: A retrospective charts and neuroimaging reports review was undertaken in 177 children with chronic ataxia. Neuroimaging in 130 of 177 patients was also reviewed. Results: Nineteen patients had head computed tomography only, 103 brain magnetic resonance imaging only, and 55 had both. Abnormalities in the cerebellum or other brain regions were associated with ataxia. Neuroimaging was helpful in 73 patients with 30 disorders: It was diagnostic in 9 disorders, narrowed down the diagnostic possibilities in 14 disorders, and revealed important but non-diagnostic abnormalities, e.g. cerebellar atrophy in 7 disorders. Having a normal magnetic resonance imaging scan was mostly seen in genetic diseases or in the early course of ataxia telangiectasia. Repeat neuroimaging, performed in 108 patients, was generally helpful in monitoring disease evolution and in making a diagnosis. Neuroimaging was not directly helpful in 36 patients with 10 disorders or by definition the 55 patients with unknown disease etiology. Conclusions: Normal or abnormal neuroimaging findings and repeat neuroimaging are very valuable in the diagnosis and management of disorders associated with pediatric chronic ataxia.

Background: Hereditary spastic paraplegia (HSP) is a neurodegenerative disease that is characterized by progressive weakness and spasticity of the lower extremities; HSP can present as complicated forms with additional neurological signs. More than 70 disease loci have been described with different modes of inheritance. Methods: In this study, nine subjects from a Chinese family that included two individuals affected by HSP were examined through detailed clinical evaluations, physical examinations, and genetic tests. Targeted exome capture technology was used to identify gene mutations. Results: Two novel compound heterozygous mutations in the SPG 11 gene were identified, c.4001_4002insATAAC and c.4057C>G. The c.4001_4002insATAAC mutation leads to a reading frame shift during transcription, resulting in premature termination of the protein product. The missense mutation c.4057C>G (p.H1353D) is located in a highly conserved domain and is predicted to be a damaging substitution. Conclusions: Based on the results described here, we propose that these novel compound heterozygous mutations in SPG 11 are the genetic cause of autosomal recessive HSP in this Chinese family.

Human rabies encephalitis is rare in Canada, with only five cases reported in the past 30 years. The first and only patient who contracted rabies encephalitis in British Columbia died in 2003. Here we provide the first detailed clinical and pathological description of that case, which had several unusual features, including preexisting immunosuppression, paralytic presentation, prolonged survival, focal lesions on neuroimaging and severe neuropathology with focal necrosis, intense inflammation, and abundant viral inclusion bodies.