The optimal timing of anticoagulation after ischemic stroke in atrial fibrillation (AF) patients is unknown. Our aim was to demonstrate the feasibility and safety of initiating dabigatran therapy within 14 days of transient ischemic attack (TIA) or minor stroke in AF patients.

A prospective, multi-center registry (NCT02415855) in patients with AF treated with dabigatran within 14 days of acute ischemic stroke/TIA (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) onset. Baseline and follow-up computed tomography (CT) scans were assessed for hemorrhagic transformation (HT) and graded by using European Cooperative Acute Stroke Study criteria.

One hundred and one patients, with a mean age of 72.4 ± 11.5 years, were enrolled. Median infarct volume was 0 ml. Median time from index event onset to dabigatran initiation was 2 days, and median baseline NIHSS was 1. Pre-treatment HT was present in seven patients. No patients developed symptomatic HT. On the day 7 CT scan, HT was present in six patients (one progressing from baseline hemorrhagic infarction type 1). Infarct volume was a predictor of incident HT (odds ratio = 1.063 [1.020–1.107], p < 0.003). All six (100%) patients with new/progressive HT were functionally independent (modified Rankin Scale (mRS) = 0–2) at 30 days, which was similar to those without HT (90%, p = 0.422). Recurrent ischemic events occurred within 30 days in four patients, two of which were associated with severe disability and death (mRS 5 and 6, respectively).

Early dabigatran treatment did not precipitate symptomatic HT after minor stroke. Asymptomatic HT was associated with larger baseline infarct volumes. Early recurrent ischemic events may be clinically more important.

Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke.

We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery.

We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone.

Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%.

The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.

Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment.

Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls.

For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079).

EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.

Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada.

We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers.

Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT).

Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.

The current American Heart Association guidelines for acute ischemic stroke reserve Grade 1A recommendation for the use of endovascular thrombectomy (EVT) for patients with an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of ≥6.

We aim to determine the safety and efficacy of EVT for large vessel occlusion ischemic stroke patients with low ASPECTS (5 or less).

Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for studies appraising the outcomes of EVT for low ASPECTS ischemic stroke. A meta-analysis of proportions compared the clinical outcomes of patients undergoing EVT and those receiving best medical therapy only.

Nine studies (1,196 patients) were included. There was a trend (p = 0.11) toward a higher rate of symptomatic intracranial hemorrhage (sICH) in the EVT group (9.2%; 95% CI 6.1–13.6; I2 53.37%) compared to the medical group (5.5%; 95% CI 3.7–8.1; I2 0%). There was no difference (p = 0.41) in the pooled 90-day mortality of EVT patients (30.7%; 95% CI 21.7–41.5; I2 84.23%) and medical patients (36.6%; 95% CI 26.4–48.1; I2 76.2%). EVT patients had better (p = 0.001) 90-day outcomes, with 27.7% (95% CI 21.8–34.5; I2 62.08%) of patients attaining a modified Rankin Scale of 0–2 compared to only 3.7% (95% CI 2.3–5.9; I2 87.21%) in the medical group.

This meta-analysis demonstrates a trend in higher sICH among low ASPECTS patients undergoing EVT. Despite this, a significant proportion of this subset of patients still achieved good functional outcomes at 90 days. Randomized trials are necessary to substantiate this result as significant bias is inherent in the observational studies included in this review.

To evaluate the effectiveness and tolerability of brivaracetam (BRV) in a refractory epilepsy population in an outpatient clinical setting.

Retrospective medical information system review and self-report questionnaire for all patients treated with BRV until the end of 2017.

Thirty-eight patients were included, 73.7% female and mean age 36.2. The mean number of antiepileptic drugs (AEDs) for previous use was 8.9, and for current use was 2.5. Mean seizure frequency in the last 3 months was 12 per month. At 3, 6, 12, and 15 months, the 50% responder rates were 36.1%, 32%, 41.2%, and 45.5%, respectively. Patients took BRV for a median duration of 8.25 months, ranging from 7 days to 60 months. Retention rate was 75.0%, 72.0%, 59.2%, and 47.9% at 3, 6, 12, and 15 months, respectively. Overall, the main reasons for discontinuation were adverse events (AEs) (52.3%), lack of efficacy (35.3%), or both (11.8%). The rate of total AEs was 60.5% according to medical records and 85.7% according to questionnaire, including mostly tiredness, psychiatric, and memory complaints. Psychiatric side effects occurred in 31.6% according to medical records and 47.4% according to questionnaire results, which is higher than previously reported and persisted throughout the study period.

BRV appears to be a useful and safe add-on treatment, even in a very refractory group of patients. In this real-life clinical setting, psychiatric AEs were found at a higher rate than previously published.

Endovascular thrombectomy (EVT) is efficacious for ischemic stroke caused by proximal intracranial large-vessel occlusion involving the anterior cerebral circulation. However, evidence of its cost-effectiveness, especially in a real-world setting, is limited. We assessed whether EVT ± tissue plasminogen activator (tPA) was cost-effective when compared with standard care ± tPA at our center.

We identified patients treated with EVT ± tPA after the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing computed tomography to recanalization times trial from our prospective stroke registry from February 1, 2013 to January 31, 2017. Patients admitted before February 2013 and treated with standard care ± tPA constitute the controls. The sample size was 88. Cost-effectiveness was assessed using the net monetary benefit (NMB). Differences in average costs and quality-adjusted life years (QALYs) were estimated using the augmented inverse probability weighted estimator. We accounted for sampling and methodological uncertainty in sensitivity analyses.

Patients treated with EVT ± tPA had a net gain of 2.89 [95% confidence interval (CI): 0.93–4.99] QALYs at an additional cost of $22,200 (95% CI: −28,902–78,244) per patient compared with the standard care ± tPA group. The NMB was $122,300 (95% CI: −4777–253,133) with a 0.85 probability of being cost-effective. The expected savings to the healthcare system would amount to $321,334 per year.

EVT ± tPA had higher costs and higher QALYs compared with the control, and is likely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY.

Delayed presentation to the emergency department influences acute stroke care and can result in worse outcomes. Despite public health messaging, many young adults consider stroke as a disease of older people. We determined the differences in ambulance utilization and delays to hospital presentation between women and men as well as younger (18–44 years) versus older (≥45 years) patients with stroke.

We conducted a population-based retrospective study using national administrative health data from the Canadian Institute of Health Information databases and examined data between 2003 and 2016 to compare ambulance utilization and time to hospital presentation across sex and age.

Young adults account for 3.9% of 463,310 stroke/transient ischemic attack/hemorrhage admissions. They have a higher proportion of hemorrhage (37% vs. 15%) and fewer ischemic events (50% vs. 68%) compared with older patients. Younger patients are less likely to arrive by ambulance (62% vs. 66%, p < 0.001), with younger women least likely to use ambulance services (61%) and older women most likely (68%). Median stroke onset to hospital arrival times were 7 h for older patients and younger men, but 9 h in younger women. There has been no improvement among young women in ambulance utilization since 2003, whereas ambulance use increased in all other groups.

Younger adults, especially younger women, are less likely to use ambulance services, take longer to get to hospital, and have not improved in utilization of emergency services for stroke over 13 years. Targeted public health messaging is required to ensure younger adults seek emergency stroke care.

Large prospective observational studies have cast doubt on the common assumption that endovascular thrombectomy (EVT) is superior to intravenous thrombolysis for patients with acute basilar artery occlusion (BAO). The purpose of this study was to retrospectively review our experience for patients with BAO undergoing EVT with modern endovascular devices.

All consecutive patients undergoing EVT with either a second-generation stent retriever or direct aspiration thrombectomy for BAO at our regional stroke center from January 1, 2013 to March 1, 2019 were included. The primary outcome measure was functional outcome at 1 month using the modified Rankin Scale (mRS) score. Multivariable logistic regression was used to assess the association between patient characteristics and dichotomized mRS.

A total of 43 consecutive patients underwent EVT for BAO. The average age was 67 years with 61% male patients. Overall, 37% (16/43) of patients achieved good functional outcome. Successful reperfusion was achieved in 72% (31/43) of cases. The median (interquartile range) stroke onset to treatment time was 420 (270–639) minutes (7 hours) for all patients. The procedure-related complication rate was 9% (4/43). On multivariate analysis, posterior circulation Alberta stroke program early computed tomography score and Basilar Artery on Computed Tomography Angiography score were associated with improved functional outcome.

EVT appears to be safe and feasible in patients with BAO. Our finding that time to treatment and successful reperfusion were not associated with improved outcome is likely due to including patients with established infarcts. Given the variability of collaterals in the posterior circulation, the paradigm of utilizing a tissue window may assist in patient selection for EVT. Magnetic resonance imaging may be a reasonable option to determine the extent of ischemia in certain situations.

Although cognitive deficits are frequent in multiple sclerosis (MS), screening for them with tools such as the Montreal Cognitive Assessment (MoCA) test is usually not performed unless there is a subjective complaint. The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is among the instruments most commonly used to assess self-reported subjective complaints in MS. Nonetheless, it does not always accurately reflect cognitive status; many patients with cognitive deficits thus fail to receive appropriate referral for detailed neuropsychological evaluation. The objective of this study was to examine the validity of the MoCA test to detect the presence of objective cognitive deficits among patients with MS without subjective complaints using the Minimal Assessment of Cognitive Function in MS (MACFIMS) as the gold standard.

The sample included 98 patients who were recruited from a university hospital MS clinic. The MSNQ was used to select patients without subjective cognitive complaints who also completed the MACFIMS, MoCA test and MSQOL-54.

23.5% of patients without subjective cognitive complaints had evidence of objective cognitive impairment on the MACFIMS (z score < -1.5 on two or more tests). The MoCA had a sensitivity of 87% and a specificity of 68% for detecting objective cognitive impairment in this patient population using a cut-off score of 27.

A significant proportion of patients without self-reported cognitive impairment do have evidence of cognitive deficits on more exhaustive cognitive assessment. The MoCA is a rapid screening test that could be used to target patients for whom a more detailed neuropsychological assessment would be recommended.

The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT.

We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (<6 hours from onset) and late (≥6 hours from onset or last time seen normal) window groups. Incidence of symptomatic hemorrhagic transformations (sHTs) at 24 hours and 3-month modified Rankin scores (mRSs) were compared.

During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15–23] vs. late: 17 [13–21]), as were median ASPECT scores (early: 9 [8–10] vs. late: 9 [7–9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0–2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76).

NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.

In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.

Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.

Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.

In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.

Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system.

An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service.

The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be “evidence-based” and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future.

This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.

Traumatic brain injury (TBI) is a leading cause of death and disability. Risk factors for in-hospital mortality include older age, co-morbidity, and TBI severity. Few studies have investigated the role of sepsis in individuals with TBI.

We studied adult patients with TBI admitted to intensive care over a 5-year period. Patient characteristics were identified by linking clinical and administrative databases. Charts of individuals with TBI and sepsis were manually reviewed. Predictors of ICU and hospital mortality were identified using logistic regression modeling.

Four hundred eighty-six individuals with TBI were admitted to intensive care. Sixteen (3.3%) developed sepsis. Pneumonia was the most common source (94%). Staphylococcus aureus was the most common pathogen (75%). ICU lengths of stay (LOS) (12.2 days [interquartile range (IQR) 4.4–23.5] versus 3.7 days [IQR 1.7–8.2]; p < 0.001) and hospital LOS (28.0 days [IQR 11.8–41.4] versus 15.3 days [IQR 5.0–30.9]; p = 0.017) were longer in patients with TBI and sepsis. Sepsis was not associated with ICU (adjusted odds ratio [aOR] 0.51; 95%CI 0.12–2.27; p = 0.38) or hospital (aOR 0.78; 95% CI 0.21–2.96; p = 0.78) mortality, though age (aOR 1.02; 95% CI 1.00–1.04; p = 0.014 for hospital mortality), severe TBI (aOR 3.71; 95% CI 1.52–9.08; p = 0.004 for ICU mortality and 4.10; 95% CI 1.95–8.65; p < 0.001 for hospital mortality), and APACHE II score (aOR 1.19; 95% CI 1.11–1.28; p < 0.001 for ICU mortality and 1.22; 95% CI 1.14–1.31; p < 0.001 for hospital mortality) were.

Sepsis in patients with TBI was not associated with mortality; however, sepsis was associated with increased health care utilization (ICU and hospital LOS).

Intravenous tissue-type plasminogen activator (IVtPA) is a proven treatment for acute ischemic stroke; however, diabetes mellitus (DM) and previous cerebral infarction (PCI) were considered relative contraindications for thrombolysis within the 3–4.5 h period.

The study aimed to determine the safety and efficacy of IVtPA among diabetic patients with PCI presenting with acute ischemic stroke.

Studies which evaluated the outcome of IVtPA in terms of symptomatic intracerebral hemorrhage (sICH), functional outcome in modified Rankin scale, and death among diabetic patients with PCI presenting with acute ischemic stroke within the 3–4.5 h period were systematically searched until July 2019. Screening and eligibility criteria were applied. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Odds ratios (ORs) with 95% confidence interval (CI) were used to compare measures of treatment effect. Mantel–Haenszel method and random-effects model were also employed.

Four registry-based studies with a total of 44,572 patients were included for quantitative synthesis. Giving IVtPA among DM+/PCI+ patients did not result in significantly increased rate of sICH (OR, 1.09; 95% CI, 0.88, 1.36) compared to No DM+/PCI+ patients. However, there was significantly higher mortality (OR, 1.81; 95% CI, 1.60, 2.06) in the DM+/PCI+ group. Conversely, among those who survived, the DM+/PCI+ patients were more functionally independent at 3 months (OR, 0.76; 95% CI, 0.61, 0.94).

Limited evidence suggests that thrombolysis in DM+/PCI+ patients does not result in significantly higher incidence of sICH and may improve functional independence. However, the significantly higher mortality in this group warrants an assessment of the individualized risk–benefit ratio in the use of IVtPA.

Post-cardiac surgery patients exhibit a higher incidence of postoperative delirium (PD) compared to non-cardiac surgery patients. Patients with various cardiac diseases suffer from preoperative sleep disorder (SPD) induced by anxiety, depression, breathing disorder, or other factors.

To examine the effect of sleep disorder on delirium in post-cardiac surgery patients.

We prospectively selected 186 patients undergoing selective cardiac valve surgery. Preoperative sleep quality and cognitive function of all eligible participants were assessed through the Pittsburgh Sleep Quality Index (PSQI) and the Montreal Cognitive Assessment, respectively. The Confusion Assessment Method for Intensive Care Unit was used to assess PD from the first to seventh day postoperatively. Patients were divided into two groups according to the PD diagnosis: (1) No PD group and (2) the PD group.

Of 186 eligible patients, 29 (15.6%) were diagnosed with PD. A univariate analysis showed that gender (p = 0.040), age (p = 0.009), SPD (p = 0.008), intraoperative infusion volume (p = 0.034), postoperative intubation time (p = 0.001), and intensive care unit stay time (p = 0.009) were associated with PD. A multivariate logistic regression analysis demonstrated that age (odds ratio (OR): 1.106; p = 0.001) and SPD (OR: 3.223; p = 0.047) were independently associated with PD. A receiver operating characteristic curve demonstrated that preoperative PSQI was predictive of PD (area under curve: 0.706; 95% confidence interval: 0.595–0.816). A binomial logistic regression analysis showed that there was a significant association between preoperative 6 and 21 PSQI scores and PD incidence (p = 0.009).

Preoperative SPD was significantly associated with PD and a main predictor of PD.