Jennifer J. Majersik

Ambient air pollution and risk for ischemic stroke and transient ischemic attack

Data on the association between air pollution and cerebrovascular disease in the United States are limited. The objective of this study was to investigate the association between short‐term exposure to ambient air pollution and risk for ischemic cerebrovascular events in a US community.

Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection

Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defined by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass effect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be difficult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confirm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10−3; combined P = 1.00 × 10−11). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Acute Stroke Symptoms. Comparing Women and Men

Background and Purpose— In a recent meta-analysis, women with stroke had 30% lower odds of receiving tissue plasminogen activator than did men, and some studies have reported greater in-hospital delays in women with stroke. Causes of these disparities are unclear but could result from a different symptom presentation in women. Our objective was to prospectively investigate gender differences in acute stroke symptoms. Methods— Ischemic stroke/TIA cases presenting to the University of Michigan Hospital (January 2005 to December 2007) were identified. Stroke/TIA symptoms, ascertained by patient interview, were classified as traditional or nontraditional (pain, mental status change, lightheadedness, headache, other neurological, nonneurological). Prevalence of any nontraditional symptom and of each symptom were calculated by gender. Logistic regression was used to compare nontraditional symptoms by gender adjusted for stroke vs TIA, proxy use, age, and discharge disposition (home vs other). Results— Included were 461 cases (48.6% women; median age, 67). Among women, 51.8% reported ≥1 nontraditional stroke/TIA symptom compared to 43.9% of men (P=0.09). The most prevalent nontraditional symptom was mental status change (women, 23.2%; men, 15.2%; P=0.03). The odds of reporting at least 1 nontraditional stroke/TIA symptom were 1.42 times (95% CI, 0.97–2.06) greater in women than in men. Conclusion— A high prevalence of nontraditional symptoms among both genders was found, with women more likely to report nontraditional symptoms and, in particular, altered mental status, compared with men. Larger-scale studies focusing on stroke in women are warranted and could confirm gender differences in symptoms in a larger, more representative stroke population and address the clinical consequences.

The Causative Classification of Stroke system: an international reliability and optimization study.

Background: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. Methods: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. Results: The κ value for causative classification was 0.80 (95% confidence interval [CI] 0.78–0.81) for the 5-subtype, 0.79 (95% CI 0.77–0.80) for the 8-subtype, and 0.70 (95% CI 0.69–0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: κ = 0.81 (95% CI 0.79–0.82) for the 5-subtype, 0.79 (95% CI 0.77–0.80) for the 8-subtype, and 0.79 (95% CI 0.78–0.80) for the 16-subtype CCS. The κ value for phenotypic classification was 0.79 (95% CI 0.77–0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93–0.98) for cardioembolism, 0.88 (95% CI 0.85–0.91) for small artery occlusion, and 0.79 (0.76–0.82) for other uncommon causes. Conclusions: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras.

Severe neurotoxicity associated with exposure to the solvent 1-bromopropane (n-propyl bromide)

Background. 1-Bromopropane was recently substituted for traditional ozone-depleting solvents in the industrial setting. Case series. We report a cohort of six cases of 1-bromopropane neurotoxicity occurring in foam cushion gluers exposed to 1-bromopropane vapors from spray adhesives. Patients 1–5 were exposed 30–40 hours per week over three years; patient 6 had been employed for the previous three months. Exposure had peaked over the previous month when ventilatory fans were turned off. All patients complained of subacute onset of lower extremity pain or paresthesias. Five of six complained of difficulty walking and on examination had spastic paraparesis, distal sensory loss, and hyperreflexia. Three patients initially had nausea and headache. Serum bromide concentrations ranged from 44 to 170 mg/dL (reference 0–40 mg/dL). Apparent hyperchloremia was present with serum chloride concentrations of 105 to 139 mmol/L (reference 98–107 mmol/L). Air samples taken at the workplace during gluing operations revealed the mean air concentration of 1-bromopropane to be 130 ppm (range 91–176 ppm) with a seven hour time-weighted average of 108 ppm (range 92–127 ppm), well above the EPA-proposed limit of 25 ppm. Two years after exposure, the two most severely affected patients had minimal improvement of function and they, with a third patient, continued to experience chronic neuropathic pain. Conclusion. This report supports the growing recognition of 1‐bromopropane neurotoxicity in humans consisting most commonly of headache, nausea, and subacute spastic paraparesis with distal sensory loss. The pathogenesis of 1-BP neurotoxicity in humans has yet to be fully elucidated but may reflect a central distal axonopathy syndrome.

Population-Based Analysis of the Impact of Expanding the Time Window for Acute Stroke Treatment

Background and Purpose— Currently, a major focus on expanding acute ischemic stroke treatment opportunities centers on the development of drugs and devices with longer time windows for use. We sought to determine the time intervals within which stroke patients present to establish whether time window expansion will translate into more treatment. Methods— Data were derived from the Brain Attack Surveillance in Corpus Christi project, a population-based stroke surveillance study in an urban, southeast Texas county. This community does not contain an academic medical center, thus providing a “real-world” setting to capture patient arrival times. Onset time was recorded from the chart according to a prespecified methodology. Results— From January 2000 to June 2005, 2347 patients with acute ischemic stroke were validated. The mean age was 71 years, and 53% were female. Thirty-one percent presented within 3 hours of symptom onset; 13% between 3 and 6 hours; and 15% between 6 and 12 hours. Forty-one percent presented beyond 12 hours from symptom onset. Nearly half of patients with moderate and severe strokes presented in the 0- to 3-hour time window, whereas only 28% of mildly affected patients presented early. Conclusions— This population-based study provides estimates of time to presentation in a representative community without tertiary referral bias. These data are useful for planning acute stroke therapy interventions and suggest that in addition to developing therapies with expanded time windows, research resources should also be devoted to reducing hospital presentation delays.

Telemedicine Quality and Outcomes in Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— Telestroke is one of the most frequently used and rapidly expanding applications of telemedicine, delivering much-needed stroke expertise to hospitals and patients. This document reviews the current status of telestroke and suggests measures for ongoing quality and outcome monitoring to improve performance and to enhance delivery of care. Methods— A literature search was undertaken to examine the current status of telestroke and relevant quality indicators. The members of the writing committee contributed to the review of specific quality and outcome measures with specific suggestions for metrics in telestroke networks. The drafts were circulated and revised by all committee members, and suggestions were discussed for consensus. Results— Models of telestroke and the role of telestroke in stroke systems of care are reviewed. A brief description of the science of quality monitoring and prior experience in quality measures for stroke is provided. Process measures, outcomes, tissue-type plasminogen activator use, patient and provider satisfaction, and telestroke technology are reviewed, and suggestions are provided for quality metrics. Additional topics include licensing, credentialing, training, and documentation.

Provider perceptions of barriers to the emergency use of tPA for Acute Ischemic Stroke: A qualitative study

BackgroundOnly 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care.MethodsTwenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist).ResultsThe following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines.ConclusionsHealthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful.Trial RegistrationClinicalTrials.gov identifier: NCT00349479

Endovascular therapy for acute ischaemic stroke: a systematic review and meta-analysis of randomized trials

AIMS Evidence from randomized controlled trials (RCTs) evaluating possible benefits of endovascular therapy (EVT) for acute ischaemic stroke has shown conflicting results. The purpose of this meta-analysis was to systematically examine clinical outcomes in RCTs comparing the use of intravenous (IV) fibrinolysis alone to IV fibrinolysis plus EVT, for the treatment of acute ischaemic stroke. METHODS AND RESULTS We selected English language RCTs, comparing EVT plus IV tissue-type plasminogen activator (tPA) (if eligible) with IV tPA alone in eligible patients for the treatment of acute ischaemic stroke. The primary endpoint was good functional outcome [modified Rankin Scale (mRS) of 0-2]. Other major endpoints of interest were all-cause mortality and symptomatic intracerebral haemorrhage (sICH). The meta-analysis included 8 RCTs that randomized 2423 patients with large-vessel, anterior-circulation stroke. EVT significantly improved the rate of functional independence (90-day mRS of 0-2) when compared with IV fibrinolysis [odds ratio (OR) 1.73, 95% confidence interval (CI) 1.18-2.53, number needed to treat (NNT) = 9.3]. The all-cause mortality was lower with EVT compared with the control group; however, the result did not reach statistical significance (OR 0.89, 95% CI 0.68-1.15). The rate of sICH was not higher with EVT (OR 1.07, 95% CI 0.73-1.56). Analyses from only the recent trials (reported in 2014-15) showed further benefit (OR of mRS 0-2: 2.42, 95% CI 1.91-3.08, NNT = 5) with similar safety results. CONCLUSION In centres with advanced systems of stroke care, EVT significantly improved functional outcomes (without compromising safety) in patients with acute ischaemic stroke due to anterior circulation, large artery occlusion, compared with standard therapy.