Charlotte Zerna

Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHAs Lifes Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index <25 kg/m2) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimers Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHAs Lifes Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHAs Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention.

Cerebral Amyloid Angiopathy Is Associated With Executive Dysfunction and Mild Cognitive Impairment

Background and Purpose— Autopsy studies suggest that cerebral amyloid angiopathy (CAA) is associated with cognitive impairment and risk for dementia. We analyzed neuropsychological test data from a prospective cohort study of patients with CAA to identify the prevalence of cognitive impairment and its associations with brain magnetic resonance imaging features and the apolipoprotein E genotype. Methods— Data were analyzed from 34 CAA, 16 Alzheimer’s disease, 69 mild cognitive impairment, and 27 ischemic stroke participants. Neuropsychological test results were expressed as z scores in relation to normative data provided by the test manuals and then grouped into domains of memory, executive function, and processing speed. Results— Mean test scores in CAA participants were significantly lower than norms for memory (−0.44±1.03; P=0.02), executive function (−1.14±1.07; P<0.001), and processing speed (−1.06±1.12; P<0.001). Twenty-seven CAA participants (79%) had mild cognitive impairment based on low cognitive performance accompanied by cognitive concerns. CAA participants had similarly low executive function scores as Alzheimer’s disease, but relatively preserved memory. CAA participants’ scores were lower than those of ischemic stroke controls for executive function and processing speed. Lower processing speed scores in CAA were associated with higher magnetic resonance imaging white matter hyperintensity volume. There were no associations with the apolipoprotein E &egr;4 allele. Conclusions— Mild cognitive impairment is very prevalent in CAA. The overall cognitive profile of CAA is more similar to that seen in vascular cognitive impairment rather than Alzheimer’s disease. White matter ischemic lesions may underlie some of the impaired processing speed in CAA.

Multiphase CT angiography increases detection of anterior circulation intracranial occlusion

Objective: To evaluate whether the use of multiphase CT angiography (CTA) improves interrater agreement for intracranial occlusion detection between stroke neurology trainees and an expert neuroradiologist. Methods: A neuroradiologist and 2 stroke neurology fellows independently reviewed 100 prospectively collected single-phase and multiphase CTA scans from acute ischemic stroke patients with mild symptoms (NIH Stroke Scale score ≤5). The presence and location of a vascular occlusion(s) were documented. Interrater agreement single- and multiphase CTA was quantified using unweighted κ statistics. We assessed for any occlusions, anterior vs posterior occlusions, and pial vessel asymmetry. Results: Using multiphase CTA, the neuroradiologist detected 50 scans with anterior circulation occlusions and 15 scans with posterior circulation occlusions. Median reading time was 2 minutes per scan. Median reading time for the neurologists was 3 minutes per multiphase CTA scan. Interrater agreement was fair between the 2 neurologists and neuroradiologist when using single-phase CTA (κ = 0.45 and 0.32). Agreement improved minimally when stratified by anterior vs posterior circulation. When using multiphase CTA, agreement was high for detection of occlusion or asymmetry of pial vessels in the anterior circulation (κ = 0.80 and 0.84). Conclusions: Multiphase CTA improves diagnostic accuracy in minor ischemic stroke for detection of anterior circulation intracranial occlusion. Classification of evidence: This study provides Class II evidence that multiphase CTA, compared to single-phase CTA, improves the interrater agreement between stroke neurology trainees and an expert neuroradiologist for detecting anterior circulation intracranial vascular occlusion in patients with minor acute ischemic strokes.

Imaging, Intervention, and Workflow in Acute Ischemic Stroke: The Calgary Approach

SUMMARY: Five recently published clinical trials showed dramatically higher rates of favorable functional outcome and a satisfying safety profile of endovascular treatment compared with the previous standard of care in acute ischemic stroke with proximal anterior circulation artery occlusion. Eligibility criteria within these trials varied by age, stroke severity, imaging, treatment-time window, and endovascular treatment devices. This focused review provides an overview of the trial results and explores the heterogeneity in imaging techniques, workflow, and endovascular techniques used in these trials and the consequent impact on practice. Using evidence from these trials and following a case from start to finish, this review recommends strategies that will help the appropriate patient undergo a fast, focused clinical evaluation, imaging, and intervention.

Use and Utility of Administrative Health Data for Stroke Research and Surveillance

Despite declining age-standardized stroke incidence in high-income countries, stroke incidence is rising in low- and middle-income countries.1 Globally, the absolute burden of stroke was high in 2010 with 16.9 million first-ever strokes, 5.9 million stroke-related deaths, and 102 million disability-adjusted life-years lost.1 These numbers are projected to increase. Surveillance provides an understanding of stroke frequency, burden, distribution, and determinants. These data are essential for monitoring trends over time, guiding judicious resource allocation, and for the design, implementation, and evaluation of interventions aimed at stroke prevention, treatment, and rehabilitation.2 Collecting data specifically for research purposes can be costly and time-consuming, limiting the sample size, period of follow-up, and geographical distribution of subjects. Surveillance requires continuous data collection in large geographic areas over years; therefore, attention has been paid to secondary use data. Health services utilization data, or administrative health data, provide a wealth of information for health services researchers and for stroke surveillance. However, the information collected and ascertainment methods are heterogeneous between countries and even between jurisdictions within a country, making the data vulnerable to selection and measurement bias. Comparing international data is also challenging.3 In this review, we discuss the strengths and weaknesses of administrative health data for stroke surveillance. Administrative health data are routinely generated through interactions with healthcare systems. They are collected for payment, monitoring, planning, priority setting, and evaluation of health services provision. Sources include, but are not limited to, hospitalizations, emergency department and ambulatory care visits, and physician billings. Unlike prospective clinical research data collection, administrative health data are accumulated in a distributed manner over a prolonged period of time. As a result, these data capture a large number of individuals and a wide range of demographic information, including race/ethnicities, geographical areas (eg, rural versus urban), and institutions (eg, community versus …

Improving Door-to-Needle Times for Acute Ischemic Stroke: Effect of Rapid Patient Registration, Moving Directly to Computed Tomography, and Giving Alteplase at the Computed Tomography Scanner

Background— The effectiveness of specific systems changes to reduce DTN (door-to-needle) time has not been fully evaluated. We analyzed the impact of 4 specific DTN time reduction strategies implemented prospectively in a staggered fashion. Methods and Results— The HASTE (Hurry Acute Stroke Treatment and Evaluation) project was implemented in 3 phases at a single academic medical center. In HASTE I (June 6, 2012 to June 5, 2013), baseline performance was analyzed. In HASTE II (June 6, 2013 to January 24, 2015), 3 changes were implemented: (1) a STAT stroke protocol to prenotify the stroke team about incoming stroke patients; (2) administering alteplase at the computed tomography (CT) scanner; and (3) registering the patient as unknown to allow immediate order entry. In HASTE III (January 25, 2015 to June 29, 2015), we implemented a process to bring the patient directly to CT on the emergency medical services stretcher. Log-transformed DTN time was modeled. Data from 350 consecutive alteplase-treated patients were analyzed. Multivariable regression showed the following factors to be significant: giving alteplase in the CT (32% decrease in DTN time, 95% confidence interval [CI] 38%–55%), stretcher to CT (30% decrease in DTN time, 95% CI 16%–42%), patient registered as unknown (12% decrease in DTN time, 95% CI 3%–20%), STAT stroke protocol (11% decrease in DTN time, 95% CI 1%–20%), and stroke severity (National Institutes of Health Stroke Scale score 6–8: 19% decrease in DTN time, 95% CI 6%–31%; National Institutes of Health Stroke Scale score >8: 27% decrease in DTN time, 95% CI 17%–37%). Conclusions— Taking the patient to CT on the emergency medical services stretcher, registering the patient as unknown, STAT stroke protocol, and administering alteplase in CT are associated with lower DTN time.

Evolving Treatments for Acute Ischemic Stroke

The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment.

The Effects of Pretreatment versus De Novo Treatment with Selective Serotonin Reuptake Inhibitors on Short-term Outcome after Acute Ischemic Stroke

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) administered in patients following acute ischemic stroke have shown to improve clinical recovery independently of changes in depression. Animal studies have demonstrated that sustained SSRI treatment is superior to short-term SSRI in evoking neurogenesis but how this benefit translates into humans remains to be answered. We hypothesized that in acute ischemic stroke patients, SSRI treatment started before the event leads to improved short-term outcomes compared to de novo SSRI treatment poststroke. METHODS We performed an exploratory analysis in consecutive acute ischemic stroke patients and compared patients already receiving fluoxetine, citalopram, or escitalopram with those who started treatment de novo. RESULTS Of 2653 screened patients, 239 were included (age, 69 ± 14 years; 42% men, baseline median National Institutes of Health Stroke Scale score, 7 [IQR, 10]). Of these patients, 51 started treatment with SSRI before stroke and 188 were prescribed newly SSRIs during hospitalization. In the adjusted multivariate logistic regression models, SSRI pretreatment was associated with favorable functional outcome at discharge defined as a modified Rankin Scale score of 2 or less (odds ratio [OR], 4.00; 95% confidence interval [CI], 1.68-9.57; P < .005), improved early clinical recovery (OR, 2.35; 95% CI, 1.15-4.81; P = .02), and a trend toward prediction of superior motor recovery (OR, 1.82; 95% CI, .90-3.68; P < .01). CONCLUSIONS Our data suggest that SSRI pretreatment may improve clinical outcomes in the early stages of acute ischemic stroke supporting the hypothesis that prolonged SSRI treatment started prestroke is superior to poststroke SSRI.

Cerebral Microbleeds and Cortical Superficial Siderosis in Patients Presenting With Minor Cerebrovascular Events

Background and Purpose— Transient focal neurological episodes occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Risk factors and outcomes of minor ischemic stroke or TIA might differ in patients with and without cerebral microbleeds (CMBs), including CAA-consistent lobar CMB. Methods— Baseline magnetic resonance imaging (MRI) was analyzed for CMBs and cortical superficial siderosis in 416 patients in the prospective computed tomography and MRI in the CATCH study (Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Clinical symptoms, baseline characteristics, recurrence, and 90-day modified Rankin Scale were prospectively collected. MRI white-matter hyperintensity was measured using the Fazekas scale. Results— CMBs were detected in 65 (15.6%) and cortical superficial siderosis in 11 patients (2.6%). Lobar CMBs were present in 49 (11.8%). In multivariable logistic regression adjusted for risk factors and age, subcortical Fazekas score was associated with lobar CMB (odds ratio, 2.07; 95% confidence interval, 1.23–3.48; P=0.006). Forty-two patients (10.1%) had lobar-only CMBs with or without cortical superficial siderosis consistent with modified Boston criteria for possible/probable CAA. The possible/probable CAA pattern was not predictive of recurrent TIA (odds ratio, 0.42; 95% confidence interval, 0.05–3.31; P=0.41), stroke (odds ratio, 1.24; 95% confidence interval, 0.26–5.99; P=0.79), or 90-day modified Rankin Scale score ≥2 (odds ratio, 1.38; 95% confidence interval, 0.62–3.07; P=0.42). Conclusions— CMBs in TIA and minor stroke are moderately common but do not predict recurrence or 90-day outcome. CAA-related transient focal neurological episodes and TIA have overlapping clinical symptoms, suggesting that MRI may be needed for differentiation.

Telemedical Brain Computed Tomography Misinterpretation by Stroke Neurologists Is Not Associated with Thrombolysis-Related Intracranial Hemorrhage.

BACKGROUND The Stroke Eastern Saxony Network (SOS-NET) provides telecare for acute stroke patients. Stroke neurologists recommend intravenous thrombolysis based on clinical assessment and cerebral computed tomography (CT) evaluation using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether ASPECTS misinterpretation by stroke neurologists was associated with thrombolysis-related symptomatic intracranial hemorrhage (sICH). METHODS We retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans blinded to clinical information providing reference standard. We defined ASPECTS underestimation as ASPECTS stroke neurologist--ASPECTS neuroradiologist more than 1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II criteria. Secondary outcome was unfavorable outcome at discharge defined as modified Rankin Scale scores 3 or more. RESULTS Of 1659 patients with acute ischemic stroke, thrombolysis was performed in 657 patients. Complete primary outcome and imaging data were available for 432 patients (median age, 75; interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259 patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement between ASPECTS assessment was fair (κ = .51). ASPECTS underestimation was neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95% CI, .47-2.54; P = .83). CONCLUSIONS Despite fair interrater agreement between stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by the former was not associated with thrombolysis-related sICH in our telestroke network.