Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Background: Decisions to treat large-vessel occlusion with endovascular therapy(EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ pre-stroke comorbidities. Methods: In an international survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case-scenarios. Five included comorbidities(metastatic/non-metastatic cancer, cardiac/respiratory/renal disease, non-disabling/mild cognitive impairment[MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Results: Among 607 physicians(38 countries), EVT was favoured in 1,097/1,379(79.6%) responses for comorbidity-related scenarios under current resources versus 1,510/1,657(91.1%,OR:0.38, 95%CI.0.31-0.47) for six “level-1A” scenarios (assuming ideal conditions:82.7% vs 95.1%,OR:0.25,0.19-0.33). However, this was reversed on including all other scenarios(e.g. under current resources:3,489/4,691[74.4%], OR:1.34,1.17-1.54). Responses favouring alteplase for comorbidity-related(e.g.75.0% under current resources) scenarios were comparable to level-1A scenarios(72.2%) and higher than all others(60.4%). No comorbidity-related factor independently diminished EVT-odds. MCI and dependence carried higher alteplase-odds; cancer and cardiac/respiratory/renal disease had lower odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT, lower alteplase-odds), practicing in East-Asia (higher EVT-odds), and in interventional neuroradiology(lower alteplase-odds vs neurology). Conclusions: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT.

Background: The relationship between timing of direct enteral feeding tube (DET; gastrostomy/jejunostomy) placement and outcomes after stroke is unknown. Methods: We used the Ontario Stroke Registry and linked administrative databases to identify patients with acute stroke between 2003-2013 who received DET during hospital admission. We used multiple logistic regression and Cox proportional hazard models to determine the association between time from admission to DET placement and outcomes of severe disability at discharge (modified Rankin Scale score 4-5) and 30-day mortality after DET placement, adjusting for age, sex, co-morbidities, stroke type, stroke severity, intensive care or stroke unit admission, palliation, and hospital type. Results: 1,342 patients met our inclusion criteria. There was a lower hazard of 30-day mortality for each week in delay to DET placement (adjusted HR 0.89, 95%CI 0.80 to 0.99), but higher odds of severe disability (adjusted OR 1.36, 95%CI 1.14 to 1.62). Patients with DET placement within 1 week had the highest 30-day mortality compared to subsequent weeks (adjusted HR 1.59, 95%CI 1.05 to 2.4). Conclusions: Delayed DET placement after stroke is associated with lower 30-day mortality but greater disability. Thirty-day mortality was highest in those who received DET within 1 week of admission. These associations may inform decisions regarding timing of DET placement after stroke.

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: In patients with acute stroke, nasogastric (NG) tubes are commonly inserted for feeding when dysphagia is identified, and percutaneous endoscopic gastrostomy (PEG) tubes are placed for severe or persistent dysphagia. However, little is known regarding predictors of PEG insertion. Methods: We used the Ontario stroke registry from 2003-2013 to identify baseline characteristics of all patients with NG or PEG tube insertion after stroke. We used multiple logistic regression with backwards selection to determine variables that were independent predictors of PEG tube insertion during admission. Results: 4002 patients with NG and 1903 patients with PEG were included in the analysis. Independent predictors of PEG were: Age (80+ vs. <60; odds ratio [OR] 1.70), past history of stroke (OR 1.17), higher stroke severity (severe vs. mild stroke; OR 1.37), stroke unit admission (OR 1.46), and dysphagia screening (OR 1.52). Factors associated with reduced odds of PEG insertion were: Prior history of peptic ulcer disease (OR 0.70), prior independence (OR 0.78), dementia (OR 0.76), palliative status (OR 0.49), and thrombolysis (OR 0.66). *All p<0.01 Conclusions: The strongest predictors of PEG were older age, higher stroke severity, stroke unit admission and dysphagia screening. Patients with dementia had reduced odds of PEG. Thrombolysis also reduced odds of PEG and may be protective.

Background: Dysphagia is a devastating complication of stroke and can lead to malnutrition, immobility, aspiration pneumonia, and death. Guidelines advocate screening all patients with acute stroke for swallowing impairment. However, previous research suggests only 60% are screened, and it is unclear what factors contribute to receiving dysphagia screening. Methods: We used the Ontario Stroke Registry to identify patients who were admitted to Regional Stroke Centres from 2010-2013. We used multivariable regression to identify predictors of receiving a dysphagia screen within 72 hours. Results: Among 7172 patients with acute ischemic stroke, 1705 patients (23.8%) did not undergo screening. Factors increasing the odds of being tested were: Stroke unit admission (adjusted odds ratio aOR 6.5), presenting with speech deficits (aOR 1.9) or weakness (aOR 1.5), or receiving thrombolysis (aOR 1.9). Seizure (aOR 0.49) and mild stroke (aOR 0.59 vs moderate stroke) decreased the odds of being tested. Among those with mild strokes who received a swallowing screen, 33% failed. *All p<0.0001. Conclusions: Patients with mild stroke are at risk of not being screened for dysphagia, despite a significant fail rate among those tested. This may expose untested patients to a higher risk of complications from dysphagia, and suggests a gap in process of care that should be addressed.

Background: Bedside dysphagia screening is recommended for all patients with acute ischemic stroke, in order to detect swallowing impairment early and prevent complications. However, limited data are available on outcomes associated with failing a dysphagia screen. Methods: We used the Ontario Stroke Registry to identify patients who were admitted to Regional Stroke Centres from 2010-2013 and received a dysphagia screen within 72 hours. We used multivariable regression to determine outcomes of patients who failed the dysphagia screen. Results: Among 5145 patients who underwent dysphagia screening, 2458 (47.8%) failed and 2687 (52.2%) passed. Patients who failed had more co-morbidities and presented with more severe strokes (mean NIHSS 11.0 vs. 5.4). Among those who failed, 9% required permanent feeding tubes, versus 0.1% among those who passed. After controlling for age, co-morbidities, and stroke severity, failing a bedside swallowing screen remained highly predictive of poor outcomes, including decubitus ulcer (adjusted odds ratio aOR 10.5), pneumonia (aOR 4.6), discharge to long-term care (aOR 4.1) and 30-day mortality (aOR 4.5; 16.6% vs. 2.2%). *All p <0.0001 Conclusions: Patients who failed a dysphagia screen on admission had dramatically worse outcomes after controlling for baseline factors. A bedside dysphagia screen provides immediate risk stratification for acute stroke patients and can be used to guide appropriate care.

Background: Seizures and epilepsy are well-recognized complications after stroke. However, the reported incidence varies and so does their management. Methods: We conducted a systematic review and sought observational studies that reported incidence of seizures and/or epilepsy following arterial ischemic stroke in adults, and those that reported the management of epilepsy, specifically the use of EEG to determine the diagnosis, timing of initiation of anti-epileptic drug (AED), and the treatment response to AEDs. We systematically searched in Medline including Pre-Medline and EMBASE databases from their inception to October 1, 2015. First the titles and then the articles were reviewed and rated by two independent reviewers, and disagreements were resolved by consultation with a third reviewer. A pre-set data abstraction form was used for extracting the information of interest. Results: A total of 11,815 titles were found from the initial search strategy across all databases following de-duplication. Of these 130 studies are included for full text review. The adjudication process is underway and the reviewers are sifting through these studies to select the studies that will be included in the final review. Conclusions: Understanding incidence and management of post-stroke epilepsy is important to improve the quality of life of stroke survivors.

Brain death is the irreversible lost of function of the brain including the brainstem. The presence of spontaneous or reflex movements constitutes a challenge for the neurological determination of death. We reviewed historical aspects and practical implications of the presence of spontaneous or reflex movements in individuals with brain death and postulated pathophysiological mechanisms. We identified and reviewed 131 articles on movements in individuals with confirmed diagnosis of brain death using Medline from January 1960 until December 2007, using ‘brain death’ or ‘cerebral death’ and ‘movements’ or ‘spinal reflex’ as search terms. There was no previous systematic review of the literature on this topic. Plantar withdrawal responses, muscle stretch reflexes, abdominal contractions, Lazarus's sign, respiratory-like movements, among others were described. For the most part, these movements have been considered to be spinal reflexes. These movements are present in as many as 40-50% of heart-beating cadavers. Although limited information is available on the determinants and pathophysiological mechanisms of spinal reflexes, clinicians and health care providers should be aware of them and that they do not preclude the diagnosis of brain death or organ transplantation.