Improving the Social Relevance of Experimental Stroke Models: Social Isolation, Social Defeat Stress and Stroke Outcome in Animals and Humans.

The outcome of ischemic stroke varies across socioeconomic strata, even among countries with universal health care. Emerging evidence suggests that psychosocial aspects of low socioeconomic status such as social isolation and social defeat stress interact with, and contribute to, stroke pathophysiology. However, experimental investigations of stroke rarely account for such socioeconomic influences. Social isolation in stroke survivors is associated with increased infarction volume, increased risk of post-stroke depression, and worse long-term functional outcome. Social defeat is thought to contribute significantly to chronic stress in low socioeconomic status groups and is associated with poor health outcomes. Chronic stress is also associated with worse post-stroke functional outcome and greater disability even after accounting for stroke severity, vascular risk factors, and access to acute stroke care. Experimental stroke studies which incorporate social isolation or social defeat stress have shown that both tissue and functional stroke outcome is affected by the increased expression of TNF-α and IL-6, increased glucocorticoid production, and suppression of the protooncogene bcl-2. This review explores the consequences of social isolation and social defeat stress on stroke, preclinical stroke models that have been used to investigate these factors, and possible molecular mechanisms underlying the influence of socioeconomic disparities on stroke outcome.

Geographic Access to Stroke Care Services in Rural Communities in Ontario, Canada.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Rural-Urban Differences in Stroke Risk Factors, Incidence, and Mortality in People With and Without Prior Stroke.

Background Rural residence is associated with stroke incidence and mortality, but little is known about potential rural/urban differences in ambulatory stroke care. Methods and Results We used the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) cohort, created from linked administrative databases from the province of Ontario, Canada, and divided into primary (N=6 207 032) and secondary (N=75 823) prevention cohorts based on the absence or presence of prior stroke. We defined rural communities as those with a population size of ≤10 000 and within each of the primary and secondary prevention cohorts, compared cardiovascular risk factors and care between rural and urban areas. We then calculated sex-/age-standardized rates of stroke incidence and mortality per 1000 person-years between January 1, 2008 and December 31, 2012 and used cause-specific hazard models to compare outcomes in rural versus urban areas adjusting for age, sex, income, ethnicity, smoking, physical activity and comorbid conditions, and accounting for the competing risk of death in the model for the occurrence of stroke incidence. In the primary prevention cohort, rural residents were less likely than urban ones to be screened for diabetes mellitus (70.9% versus 81.3%) and hyperlipidemia (66.2% versus 78.4%) and less likely to achieve diabetes mellitus control (hemoglobin A1c ≤7% in 51.3% versus 54.3%; P<0.001 for all comparisons). In the secondary prevention cohort, the prevalence and treatment of risk factors were similar in rural and urban residents. After adjustment for sociodemographic and comorbid conditions, rural residence was associated with higher rates of stroke and all-cause mortality in both the primary prevention (adjusted hazard ratio [aHR] for stroke, 1.06; 95% CI, 1.04-1.09; aHR for mortality, 1.09; 95% CI, 1.08-1.10) and the secondary prevention cohort (aHR for stroke, 1.11; 95% CI, 1.02-1.19; aHR for mortality, 1.07; 95% CI, 1.03-1.11). Conclusions In this population-based study of over 6 million people with universal access to physician and hospital services, risk factors were more prevalent but less likely to be controlled in rural than in urban residents without prior stroke, whereas in those with prior stroke, risk factor prevalence and treatment were similar. Rural residence was associated with the rate of stroke and death even after adjustment for risk factors. Future efforts should focus not only on control of known vascular risk factors but also on addressing other determinants of health in rural communities.

Robotic exoskeleton assessment of transient ischemic attack.

We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA). A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS) score, Chedoke-McMaster Stroke Assessment (CMSA) of the arm, the Behavioural Inattention Test (BIT), the Purdue pegboard test (PPB), and the Montreal Cognitive Assessment (MoCA). Age-related white matter change (ARWMC), prior infarction and cella-media index (CMI) were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5%) showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5%) participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction.

A prospective cohort study of patients with transient ischemic attack to identify high-risk clinical characteristics.

BACKGROUND AND PURPOSE: The occurrence of a transient ischemic attack (TIA) increases an individual's risk for subsequent stroke. The objectives of this study were to determine clinical features of patients with TIA associated with impending (≤7 days) stroke and to develop a clinical prediction score for impending stroke. METHODS: We conducted a prospective cohort study at 8 Canadian emergency departments for 5 years. We enrolled patients with a new TIA. Our outcome was subsequent stroke within 7 days of TIA diagnosis. RESULTS: We prospectively enrolled 3906 patients, of which 86 (2.2%) experienced a stroke within 7 days. Clinical features strongly correlated with having an impending stroke included first-ever TIA, language disturbance, longer duration, weakness, gait disturbance, elevated blood pressure, atrial fibrillation on ECG, infarction on computed tomography, and elevated blood glucose. Variables less associated with having an impending stroke included vertigo, lightheadedness, and visual loss. From this cohort, we derived the Canadian TIA Score which identifies the risk of subsequent stroke≤7 days and consists of 13 variables. This model has good discrimination with a c-statistic of 0.77 (95% confidence interval, 0.73-0.82). CONCLUSIONS: Patients with TIA with their first TIA, language disturbance, duration of symptoms≥10 minutes, gait disturbance, atrial fibrillation, infarction on computed tomography, elevated platelets or glucose, unilateral weakness, history of carotid stenosis, and elevated diastolic blood pressure are at higher risk for an impending stroke. Patients with vertigo and no high-risk features are at low risk. The Canadian TIA Score quantifies the impending stroke risk following TIA.