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.

Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

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.

Background: For optimal stroke prevention, best practices guidelines recommend carotid endarterectomy (CEA) for symptomatic patients within two weeks; however, 2013 Ontario data indicated that only 9% of eligible patients from outpatient Stroke Prevention Clinics (SPCs) achieved this target. The goal of our study was to identify modifiable system factors that could enhance the quality and timeliness of care among patients needing urgent CEA. Methods: We conducted a retrospective chart review of transient ischemic attack/stroke patients assessed in Champlain Local Health Integrated Network SPCs between 2011 and 2014 who subsequently underwent CEA. Descriptive statistics were used to define patient characteristics, timelines from symptom onset to CEA, and system factors that contributed to delays or improvements in care. Multivariate analysis was used to determine statistically significant variations between groups. Results: Seventy-five records were eligible for study inclusion. Median time from initial symptoms to CEA was 31 days, with 21.3% of patients undergoing surgery within 2 weeks. Significant delays were common in patient presentation and assessment following symptom onset, wait times for vascular imaging and neurological assessment, and time from surgical assessment to CEA completion. Rapid testing and triage, coupled with collaborative initiatives among SPC, surgical, and radiology teams were associated with significantly improved timelines. Conclusions: Success factors for rapid CEA are multifaceted, including system changes that address public awareness of stroke and 911 response, improvements in vascular imaging access, and redesign of clinical services to promote collaboration and fast-tracking of care. Implementation of performance measures to monitor and guide clinical innovations is recommended.

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.

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.

Background: The Canadian GILENYA® Go ProgramTM provides education and support to people with relapsing-remitting multiple sclerosis during fingolimod treatment. Methods: Data were collected and analyzed from the time of the first individual enrolled in March 2011 to March 31, 2014. Individuals were excluded if they withdrew from the program prior to receiving the first dose, or had not completed the first dose observation (FDO) at the time of data cut-off. Reports of adverse effects were validated with a database of adverse events reported to Novartis Pharmaceuticals Canada Inc. Results: A total of 2,399 individuals had completed FDO at the end of the three-year observation period. Mean age was 41.2 years; 75.2% were female. The most recent prior therapies reported were interferon-β agents (50.2%), glatiramer acetate (31.1%), natalizumab (14.2%), no prior therapy (3.3%), and other agent (1.1%). Reasons for switching to fingolimod were lack of efficacy (34.9%), side effects (34.6%), and dissatisfaction with injections/infusion (30.4%). Continuation rates with fingolimod at 12, 24 and 30 months were 80.7%, 76.6% and 76.0%, respectively. The discontinuation rate due to reported lack of efficacy during the three-year period was 1.3%. There was 94.4% adherence to the scheduled ophthalmic examination. Conclusions: The GILENYA® Go ProgramTM captures data for virtually all fingolimod-treated patients in Canada, enabling the evaluation of fingolimod use in routine practice. Ongoing patient support and reminders to take the medication, in conjunction with physicians’ and/or patients’ perception of the efficacy and tolerability of fingolimod, resulted in a high rate of continuation during longer-term therapy.

Multiple sclerosis is a chronic demyelinating disease characterized by focal and diffuse inflammation of the central nervous system resulting in significant physical and cognitive disabilities. Disease-modifying therapies targeting the dysfunctional immune response are most effective in the first few years after disease onset, indicating that there is a limited time window for therapy to influence the disease course. No evidence of disease activity is emerging as a new standard for treatment response and may be associated with improved long-term disability outcomes. An aggressive management strategy, including earlier use of more potent immunomodulatory agents and close monitoring of the clinical and radiologic response to treatment, is recommended to minimize early brain volume loss and slow the progression of physical and cognitive impairments in patients with relapsing-remitting multiple sclerosis.

Objective: To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias.Methods: Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer’s disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. Results: The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. Conclusions: A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.

Cerebral vasospasm is a prolonged but reversible narrowing of cerebral arteries beginning days after subarachnoid hemorrhage. Progression to cerebral ischemia is tied mostly to vasospasm severity, and its pathogenesis lies in artery encasement by blood clot, although the complex interactions between hematoma and surrounding structures are not fully understood. The delayed onset of vasospasm provides a potential opportunity for its prevention. It is disappointing that recent randomized, controlled trials did not demonstrate that the endothelin antagonist clazosentan, the cholesterol-lowering agent simvastatin, and the vasodilator magnesium sulfate improve patient outcome. Minimizing ischemia by avoiding inadequate blood volume and pressure, administering the calcium antagonist nimodipine, and intervention with balloon angioplasty, when necessary, constitutes current best management. Over the past two decades, our ability to manage vasospasm has led to a significant decline in patient morbidity and mortality from vasospasm, yet it still remains an important determinant of outcome after aneurysm rupture.

Background: Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases. Methods: We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases. Results: At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed in EOPD. Lifetime use of amantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD. Conclusions: Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD.

Background: The Brain Trauma Foundation’s 2006 surgical guidelines have objectively defined the epidural hematoma (EDH) patients who can be treated conservatively. Since then, the literature has not provided adequate clues to identify patients who are at higher risk for EDH progression (EDHP) and conversion to surgical therapy. The goal of our study was to identify those patients. Methods: We carried a retrospective review over a 5-year period of all EDH who were initially triaged for conservative management. Demographic data, injury severity and history, neurological status, use of anticoagulants or anti-platelets, radiological parameters, conversion to surgery and its timing, and Glasgow Outcome Scale were analyzed. Bivariate association and further logistic regression were used to point out the significant predictors of EDHP and conversion to surgery. Results: 125 patients (75% of all EDH) were included. The mean age was 39.1 years. The brain injury was mild in 62.4% of our sample and severe in 14.4%. Only 11.2% of the patients required surgery. Statistical comparison showed that younger age (p< 0.0001) and coagulopathy (p=0.009) were the only significant factors for conversion to surgery. There was no difference in outcomes between patients who had EDHP and those who did not. Conclusions: Most traumatic EDH are not surgical at presentation. The rate of conversion to surgery is low. Significant predictors of EDHP are coagulopathy and younger age. These patients need closer observation because of a higher risk of EDHP. Outcome of surgical conversion was similar to successful conservative management.