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.

Seizures are important complications following a subarachnoid hemorrhage (SAH). The evidence for the use of antiepileptic drugs (AEDs) in treatment and prevention of those seizures is conflicting. The purpose of this review is to provide an up-to-date evidence summary of the incidence and outcomes of seizures following an SAH as well as the use of different AEDs post-SAH in order to evaluate the need for seizure prophylaxis, the choice of AEDs, and their dosing considerations in SAH patients. A literature search of PubMed, Medline, Embase, and the Cochrane Library was performed. A total of 37 studies were reviewed, mostly observational. Definitions of seizures in temporal relation to initial hemorrhage were variable. Similarly, the rates of seizures varied in the literature, ranging from 0 to 31%. Given the reported adverse outcomes associated with AED usage, seizure prophylaxis is not warranted. Levetiracetam appears to be better tolerated than phenytoin in SAH patients, though further research is needed. Higher initial dosing of levetiracetam might be required due to its enhanced clearance in SAH patients. In conclusion, there is a lack of quality evidence to definitively recommend the use of one AED over another. Further prospective research comparing the use of different AEDs in patients with an SAH is needed.

Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients. Methods: We conducted a single-center quasi-experimental uncontrolled pre- and post-NCC study in severe traumatic brain injury patients (Glasgow Coma Scale ≤8). The NCC program includes consultation with a neurointensivist and neurosurgeon and multimodal neuromonitoring. Demographic, injury severity metrics, neurophysiologic data, and therapeutic interventions were collected. Glasgow Outcome Scale (GOS) at 6 months was the primary outcome. Multivariable ordinal logistic regression was used to model the association between NCC implementation and GOS at 6 months. Results: A total of 113 patients were identified: 76 pre-NCC and 37 post-NCC. Mean age was 39 years (standard deviation [SD], 2) and 87 of 113 (77%) patients were male. Median admission motor score was 3 (interquartile ratio, 1-4). Daily mean arterial pressure was higher (95 mmHg [SD, 10]) versus (88 mmHg [SD, 10], p<0.001) and daily mean core body temperature was lower (36.6°C [SD, 0.90]) versus (37.2°C [SD, 1.0], p=0.001) post-NCC compared with pre-NCC, respectively. Multivariable regression modelling revealed the NCC program was associated with a 2.5 increased odds (odds ratios, 2.5; 95% confidence interval, 1.1-5.3; p=0.022) of improved 6-month GOS. Conclusions: Implementation of a NCC program is associated with improved 6 month GOS in severe TBI patients.

Background: In this case series, functional magnetic resonance imaging was used to examine brain networks that mediate different aspects of language function in 4 young adults (17-22 years) with a history of left middle cerebral artery (MCA) stroke in childhood (<7 years of age but after the neonatal period), and five older individuals (42-57 years) with left MCA stroke as adults (>40 years of age). Although it is widely believed that altered lateralization patterns are more likely to occur following early brain injuries compared with later brain injuries, the presumed plasticity of the young brain has been challenged in recent years, particularly in the domain of language. Methods: We explored this issue by contrasting the brain activation patterns of individuals with childhood left MCA stroke and adult left MCA stroke while performing two language tasks: verb generation and picture-word matching. Importantly, both groups showed significant recovery of language function, based on standard clinical indicators. Results: Controls showed left lateralized activation for both tasks, although much more pronounced for verb generation. Adult stroke patients also showed left lateralization for both tasks, though somewhat weaker than controls. Childhood stroke patients exhibited significantly weaker lateralization than the adult group for verb generation, but there was no significant group difference for picture-word matching. Conclusions: These preliminary findings suggest that successful reorganization of language function is more likely to involve bilateral recruitment following left MCA stroke in childhood than in adulthood. Of importance, although childhood stroke patients had primarily subcortical lesions, there were substantial alterations in cortical activation patterns.

Background: Patients with arterial perinatal stroke often suffer long-term motor sequelae, difficulties in language, social development, and behaviour as well as epilepsy. Despite homogeneous lesions, long-term behavioural and cognitive outcomes are variable and unpredictable. Sleep-related epileptic encephalopathies can occur after early brain injury and are associated with global developmental delays. We hypothesized that sleep-potentiated epileptiform abnormalities are associated with worse developmental outcomes after perinatal stroke. Methods: Participants were identified from a population-based cohort (Alberta Perinatal Stroke Project). Inclusion criteria were magnetic resonance imaging–confirmed arterial perinatal stroke, age 4 to 18 years, electroencephalogram (EEG) including sleep, and comprehensive neuropsychological evaluation. Sleep-related EEG abnormalities were categorized by an epileptologist blinded to the cognitive outcome. Associations between EEG classification and neuropsychological outcomes were explored (t tests, Bonferroni correction for multiple comparisons). Results:Of 128 potentially eligible participants, 34 (53% female) had complete EEG (mean age, 8.1 years; range, 0.2-16.4) and neuropsychology testing (mean age, 9.8 years; range 4.4-16.7). Twelve (35%) were classified as having electrical status epilepticus in sleep. Patients with abnormal EEGs were more likely to have statistically worse scores when corrected for multiple comparisons, in receptive language (median, 1st percentile; IQR 1-7th percentile; p<0.05), and externalizing behaviours (median, 82nd percentile; IQR, 79-97th percentile; p<0.05). Conclusions: Developmental outcome in language and behaviour in children with arterial perinatal stroke is associated with electrical status epilepticus in sleep. Increased screening with sleep EEG is suggested, whereas further studies are necessary to determine if treatment of EEG abnormalities can improve outcome.

Background: In vitro models have suggested that stents affect atherosclerotic plaques symmetrically because of their outward radial forces. We evaluated the effects of stents on carotid plaque and the arterial wall using carotid ultrasound in carotid stenting patients to see whether these effects were borne out in vivo. Methods: From a carotid stent database, 30 consecutive patients were selected. All had carotid Doppler ultrasound performed pre- and poststenting. The diameters of the lumen at the level of stenotic plaque pre- and poststenting, the dorsal and ventral plaque thickness, and of the outer arterial wall diameter were measured. Plaque thickness was measured at the level of maximal stenosis. Nonparametric tests were used to determine whether the stent effect and luminal enlargement were based on wall remodeling or on total arterial expansion. Results: The patients were followed for an average of 22 months. Eighteen patients were male, with an average age of 70 years. A total of 87% of patients were symptomatic ipsilateral to the side of stenosis. Nine patients had angioplasty intraprocedurally. The luminal diameter increased poststenting in the region of severe stenosis. Plaque thickness, both ventrally and dorsally, decreased poststenting, with no significant difference between the ventral and dorsal plaque effects. The outer arterial wall diameters did not change. The measured lumen in the stent increased over time poststenting. Conclusions: Self-expanding nitinol stents alter the baseline ventral and dorsal plaque to a significant degree and do not significantly affect the native arterial wall and the overall arterial diameter.

This review aims at summarizing and discussing previous and recent findings concerning the cerebral manifestations of mitochondrial disorders (MIDs). MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) either already at onset or later in the course. After the muscle, the brain is the organ second most frequently affected in MIMODS. Cerebral manifestations of MIDs are variable and may present with or without a lesion on imaging or functional studies, but there can be imaging/functional lesions without clinical manifestations. The most well-known cerebral manifestations of MIDs include stroke-like episodes, epilepsy, headache, ataxia, movement disorders, hypopituitarism, muscle weakness, psychiatric abnormalities, nystagmus, white and gray matter lesions, atrophy, basal ganglia calcification, and hypometabolism on 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron-emission tomography. For most MIDs, only symptomatic therapy is currently available. Symptomatic treatment should be supplemented by vitamins, cofactors, and antioxidants. In conclusion, cerebral manifestations of MIDs need to be recognized and appropriately managed because they strongly determine the outcome of MID patients.

Background: Dysphagia is a common and devastating complication after acute stroke. Percutaneous endoscopic gastrostomy (PEG) tubes are often placed for persistent dysphagia. However, little is known regarding outcomes after PEG tube placement. Methods: We used a 10-year Ontario Stroke Registry to shed light on the clinical outcomes of patients with PEG tube insertion after ischemic stroke or intracranial hemorrhage compared to patients with only NG tubes, including rate of pneumonia, disability, and mortality. Results: Using propensity score matching, 1,793 patients were successfully matched and had similar baseline characteristics. Compared with NG, patients with PEG had a higher rate of pneumonia (32.6% vs. 20.6%; RR 1.59), higher disability at discharge (modified Rankin Scale Score 3-5; 74.0% vs. 65.4%; RR 1.13), and higher rate of long-term care placement (27.1% vs. 9.3%; RR 2.9). >From stroke onset, there was a lower rate of death in patients with PEG compared to NG at 30 days (15.3% vs. 34.3%; RR 0.45) but no difference at 2 years (52.8% vs. 53.5%; RR 0.99, p=0.71). *All significant p <0.0001. Conclusions: In conclusion, PEG tube placement after stroke may prolong survival in patients with poor outcomes. Our study provides a framework for discussions between physicians, patients, and families with regards to expected prognosis after PEG tube placement.

Background: More timely administration of tissue plasminogen activator (alteplase) for patients with acute ischemic stroke yields greater clinical benefits. We implemented door-to-needle (DTN) time reduction strategies at our center and evaluated their short- and long-term effects on in-hospital treatment delays and clinical outcomes. Methods: Strategies, including stroke team prenotification, direct computed tomography transfer, not routinely waiting for laboratory results and alteplase delivery on the computed tomography table, were implemented in June 2013. We included all thrombolysed patients admitted directly to our hospital between January 2012 and March 2015. In-hospital delays and symptomatic intracerebral hemorrhage rates were compared between patients pre- and postmodification, and the latter period was divided into early (first 6 months) and late (beyond 6 months) phases to assess the durability of our modifications. Results: Forty-eight individuals were treated premodification compared with 58 postmodification. The median DTN time was reduced from 75 to 46 minutes (p<0.0001). The median DTN time in the early and late postmodification phases was not significantly different (41 vs 46 minutes, p=0.4085). There was no significant difference in rates of symptomatic intracerebral hemorrhage (4.2 vs 1.7%, p=0.361) or stroke mimics (2.1 ves 5.2%, p=0.625) Conclusions: We were able to decrease our DTN time for acute stroke thrombolysis by implementing relatively simple modifications and these improvements persisted over time.

Objective: Hyperfamiliarity is a phenomenon where new stimuli are perceived as familiar. Previous studies have demonstrated familiarity disorder in mild cognitive impairment (MCI), but mostly from the perspective of a neuropsychological approach, and the exact correlation of MCI aetiologies with the phenomenon remains uncertain. Based on current evidence suggesting a frontal-subcortical pathway contributing to familiarity processing, we hypothesize that individuals with a vascular aetiology of MCI will likely suffer more familiarity deficits. This study aims to examine the real-life hyperfamiliarity symptoms in amnestic versus vascular MCI. Methods: Informants of 11 amnestic and 9 vascular cognitive impairment patients were interviewed about the frequency of hyperfamiliarity symptoms in the previous month. MRI brain images of vascular cognitive impairment patients were analysed as well. Results: Patients with vascular cognitive impairment with no dementia (VCIND) showed a significantly higher frequency of hyperfamiliarity for people but not places or objects. Within VCIND patients, overall basal ganglia hyperintensities, particularly in the putamen, were found to significantly correlate to hyperfamiliarity. Conclusions: Patients with VCIND suffer more real-life hyperfamiliarity during people recognition compared to patients with amnestic mild cognitive impairment (aMCI), despite a comparative global decline in cognitive. This is likely due to impaired memory retrieval and matching processes resulting from subcortical ischaemic lesions.

Background: Stroke patients of lower socioeconomic status have worse outcomes. It remains poorly understood whether this is due to illness severity or personal or health system barriers. We explored the experiences of stroke patients with financial barriers in a qualitative descriptive pilot study, seeking to capture perceived challenges that interfere with their poststroke health and recovery. Methods: We interviewed six adults with a history of stroke and financial barriers in Alberta, Canada, inquiring about their: (1) experiences after stroke; (2) experience of financial barriers; (3) perceived reasons for financial barriers; (4) health consequences of financial barriers; and (5) mechanisms for coping with financial barriers. Two reviewers analyzed data using inductive thematic analysis. Results: The participants developed new or worsened financial circumstances as a consequence of stroke-related disability. Poststroke impairments and financial barriers took a toll on their mental health. They struggled to access several aspects of long-term poststroke care, including allied health professional services, medications, and proper nutrition. They described opportunity costs and tradeoffs when accessing health services. In several cases, they were unaware of health resources available to them and were hesitant to disclose their struggles to their physicians and even their families. Conclusion: Some patients with financial barriers perceive challenges to accessing various aspects of poststroke care. They may have inadequate knowledge of resources available to them and may not disclose their concerns to their health care team. This suggests that providers themselves might consider asking stroke patients about financial barriers to optimize their long-term poststroke care.

Background: Few studies have tracked stroke survivors through transitions across the health system and identified the most common trajectories and quality of care received. The objectives of our study were to examine the trajectories that incident stroke patients experience and to quantify the extent to which their care adhered to the best practices for stroke care. Methods: A population-based cohort of first-ever stroke/transient ischemic attack (TIA) patients from the 2012/13 Ontario Stroke Audit was linked to administrative databases using an encrypted health card number to identify dominant trajectories (N=12,362). All trajectories began in the emergency department (ED) and were defined by the transitions that followed immediately after the ED. Quality indicators were calculated to quantify best practice adherence within trajectories. Results: Six trajectories of stroke care were identified with significant variability in patient characteristics and quality of care received. Almost two-thirds (64.5%) required hospital admission. Trajectories that only involved the ED had the lowest rates of brain and carotid artery imaging (91.5 and 44.2%, respectively). Less than 20% of patients in trajectories involving hospital admissions received care on a stroke unit. The trajectory involving inpatient rehabilitation received suboptimal secondary prevention measures. Conclusions: There are six main trajectories stroke patients follow, and adherence to best practices varies by trajectory. Trajectories resulting in patients being transitioned to home care following ED management only are least likely and those including inpatient rehabilitation are most likely to receive stroke best practices. Increased time in facility-based care results in greater access to best practices. Stroke patients receiving only ED care require closer follow-up by stroke specialists.

Background: To introduce the “uniform cortex sign” (UCS) and evaluate its performance as a diagnostic test for the presence of diffuse cortical injury (DCI). Methods: The study was approved by our institutional review board. Three experienced neuroradiologists were given a tutorial on the UCS. They were subsequently presented with 14 cases (7 control patients and 7 DCI patients with the UCS) in random order and asked to determine whether the UCS was present. Each case consisted of selected DWI, T2-weighted, and FLAIR images from unenhanced 1.5T MRI examinations. A consensus result for each case was determined by unanimity or majority rule. Results: All control patients were correctly identified as normal by all neuroradiologists (7/7). The UCS was correctly identified in 86% of DCI patients (6/7). UCS interrater agreement was high (multirater κ=0.81). Conclusions: This small study shows that the UCS can identify DCI, especially in patients with hypoxic-ischemic encephalopathy. The UCS can be subtle, hence the reader must be vigilant for this finding. The accuracy of the UCS may depend on the extent of cortical injury and time between injury and MRI. Also, a UCS may be reversible, as in our case of viral meningoencephalitis.

Purpose: We measured anterior cerebral artery (ACA)-middle cerebral artery (MCA) and posterior cerebral artery (PCA)-MCA pial filling on single-phase computed tomography angiograms (sCTAs) in acute ischemic stroke and correlate with the CTA-based Massachusetts General Hospital (MGH) and digital subtraction angiography (DSA)-based American Society of Interventional and Therapeutic Neuroradiology (ASITN) score. Methods: Patients with acute stroke and M1 MCA±intracranial internal carotid artery occlusion on baseline CTA were included. Baseline sCTA was assessed for phase of image acquisition. An evaluator assessed collaterals using the Calgary Collateral (CC) Score (measures pial arterial filling in ACA-MCA and PCA-MCA regions separately), the CTA-based MGH score, and on DSA using the ASITN score. Infarct volumes were measured on 24- to 48-hour magnetic resonance imaging/ computed tomography. Results: Of 106 patients, baseline sCTA was acquired in early arterial phase in 9.9%, peak arterial in 50.7%, equilibrium in 32.4%, early venous in 5.6%, and late venous in 1.4%. Variance in ACA-MCA collaterals explained only 32% of variance in PCA-MCA collaterals on the CC score (Spearman’s correlation coefficient rho [rho]=0.56). Correlation between ACA-MCA collaterals and the MGH score was strong (rho=0.8); correlation between PCA-MCA collaterals and this score was modest (rho=0.54). Correlation between ACA-MCA collaterals and the ASITN score was modest (n=53, rho=0.43); and correlation between PCA-MCA collaterals and ASITN score was poor (rho=0.33). Of the CTA-based scores, the CC Score (Akaike [AIC] 1022) was better at predicting follow-up infarct volumes than was the MGH score (AIC 1029). Conclusion: Collateral assessments in acute ischemic stroke are best done using CTA with temporal resolution and by assessing regional variability. ACA-MCA and MCA-PCA collaterals should be evaluated separately.

Objectives: The objectives of this study were to determine prevalence estimates of cerebral palsy (CP) among 5-year-old children in northern Alberta; to provide congenital, gestational age– and birth weight–specific, and postneonatal CP rates; and to describe motor subtypes and function. Methods: This population-based prevalence estimate study, part of the Canadian Cerebral Palsy Registry, reports confirmed CP diagnoses at age 5 years made by pediatric rehabilitation and child neurology specialists. Prevalence rates with 95% confidence intervals (CIs) used Alberta government denominators of same-age children and live births. Results: The Northern Alberta CP rate (birth years, 2008-2010) for 173 5-year-old children is 2.22 (95% CI 2.12, 2.32) per 1000 5-year-old children. The congenital CP rate is 1.99 (95% CI, 1.89-2.09) per 1000 live births; unilateral congenital CP, 1.0 (95% CI, 0.64-1.36) per 1000 live births; and postneonatal CP, 0.12 (95% CI, 0.1-0.14) per 1000 live births. Gestational age-specific rates are similar: age <28 weeks, 27.2 (95% CI, 23.05-31.35) and 28 to 31 weeks, 29.5 (95% CI, 25.78-33.22). Motor subtypes for 169 children (data missing, 4; male, 97; postnatal, 9) are: spastic, 148 (87.6%) including 31 (20.9%) with diplegia, 10 (6.8%) triplegia, 33 (22.2%) quadriplegia, 74 (50%) hemiplegia/monoplegia); and dyskinetic, 18 (10.6%) and ataxic, 3 (1.8%). A total of 107 (63.3%) ambulate without assistive devices and 111(65.7%) handle most objects with their hands independently. Conclusions: This is the fourth Canadian CP prevalence study; one from Quebec used a similar case ascertainment approach and two 1980s studies from Alberta and British Columbia used administrative databases. Northern Alberta CP rates are comparable with other developed countries. The hemiplegic subtype is the most common. Rates among preterm children have declined but are similar for the <28 and 28 to 31 gestation-week groups.

Background: Predicting epilepsy following a first seizure is difficult. Network abnormalities are observed in patients with epilepsy using resting-state functional MRI (rs-fMRI), which worsen with duration of epilepsy. We use rs-fMRI to identify network abnormalities in patients after a first seizure that can be used as a biomarker to predict development of epilepsy. Methods: Patients after a single, unprovoked seizure and age/sex matched healthy controls underwent 7 Tesla structural and resting-state functional MRI. Data were analyzed using graph theory measures. Patients were followed for development of epilepsy. Results: Nine patients and nine control subjects were analyzed. There were no differences in baseline characteristics. No patients developed epilepsy (average follow-up 3 months). No differences between groups occurred on a whole-brain network level. At a 20% threshold, significant differences occurred in the default mode network (DMN). Patients demonstrated an increased local efficiency (p=0.02) and clustering coefficient (p=0.04), and decreased path length (p=0.02) and betweenness centrality (p=0.02). Conclusions: No whole-brain network changes occur after a single unprovoked seizure. No patient has developed epilepsy suggesting this group does not have network alterations after a single seizure. In the DMN, the alterations noted indicate increased segregation of network function.

Objective: The purpose of this article is to provide a systematic review of the evidence supporting the use of milrinone for the management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). Design: Primary outcomes were functional neurological status and the incidence of cerebral infarction. Search strategies adapted to the different databases were developed by a professional librarian. Medline, EMBASE, the Cochrane Library database, Web of Science, SCOPUS, BIOSIS, Global Health, Health Star, Open SIGLE, Google Scholar and the New York Academy of Medicine Gray Literature were searched as well as clinical trials databases and the proceedings of several scientific meetings. Quality of the evidence for these outcomes across studies was adjudicated using the GRADE Working Group criteria. Results: The search resulted in 284 citations after elimination of duplicates. Of those 9 conference proceedings and 15 studies met inclusion criteria and consisted of case reports, case series and two comparative studies: one non-randomized study with physiological outcomes only and a case series with historical controls. There was considerable variation in dosing and in co-interventions and no case control or randomized controlled studies were found. Conclusion: There is currently only very low quality evidence to support the use of milrinone to improve important outcomes in patients with delayed cerebral ischemia secondary to subarachnoid hemorrhage. Further research is needed to clarify the value and risks of this medication in patients with SAH.

Objectives: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population. Methods: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team. Results: 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team. Conclusion: Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.