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Environmental genomics is a rapidly advancing field that promises to revolutionise the way in which industry conducts biodiversity monitoring. The International Association of Oil and Gas Producers Environmental Genomics Joint Industry Program (JIP) was formed in June 2019 with the aim of facilitating the development and uptake of environmental genomics within the oil and gas industry. Towards this goal, a white paper was produced that summarises the state‐of‐the‐art in environmental genomics research, and the opportunities and limitations of applying environmental genomics within industry. The white paper included a comprehensive literature review, and importantly, involved consultation with professionals from academic, regulatory and industry backgrounds from across the globe that had expertise in environmental genomics applications. While this consultation revealed a consensus that the application of environmental genomics has advanced greatly in a brief period, with demonstrable benefits, there was an acknowledgement that key aspects are still lacking that would allow confident application of genomics approaches within industry. Through the review and consultation process, a range of knowledge gaps and areas requiring further development were identified. To elucidate which of these areas were most critical to the successful application of environmental genomics within industry, the JIP is drafting guidance that describes sampling design considerations, minimum standards for laboratory analyses and approaches to genomics data interpretation. Through the drafting of guidance, the JIP hopes to determine which gaps are most critical, enabling these to be prioritised for targeted research. The guidance will then be updated regularly to capture the latest research outcomes.

Job satisfaction and retention of healthcare staff remains an ongoing issue in many health systems. Huddles have been endorsed as a mechanism to improve patient safety by improving teamwork, collaboration, and communication in teams. This study synthesizes the literature to investigate the impact of huddles on job satisfaction, teamwork, and work engagement in multidisciplinary healthcare teams. Five academic databases were searched to conduct a systematic review of peer-reviewed literature published from January 2000 – January 2020. Articles were included if they (1) featured a daily huddle, were conducted in a healthcare setting, and involved a multidisciplinary team and (2) measured variables including job satisfaction, work engagement, or teamwork. Results were reported in accordance with the Systematic Synthesis Without Meta-analysis (SWiM) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We identified 445 articles of which 12 met the eligibility criteria and are included in this review. All 12 studies found a predominantly positive impact on teamwork and job satisfaction. None of the studies discussed or reported evidence of the impact of huddles on work engagement. This review highlights the value of a daily multidisciplinary healthcare team huddle in improving job satisfaction and teamwork for the healthcare staff involved. However, there is a dearth of high-quality, peer-reviewed evidence regarding the direct impact of huddles on job satisfaction, teamwork and in particular on work engagement. Further research – particularly controlled studies on adoption, implementation, and outcomes for healthcare team culture – is needed to further assess this intervention.

Objectives Patients with TIA and minor stroke commonly undergo CT and CTA in the emergency department with subsequent MRI with MRA for further workup. The purpose of this study was to review outpatient MRIs for TIA/stroke patients to assess the additional benefit, if any, of the MRA sequence in the detection of intracranial atherosclerotic disease in patients for whom CTA had already been performed. Methods The radiology reports of outpatient MRIs of the brain for TIA/minor stroke patients were retrospectively reviewed via the hospital PACS system. Following this, the imaging report from the patient’s initial presentation to the emergency department was reviewed. This index imaging and subsequent MRI were compared to assess the incidence of new vascular findings detected on the MRA sequence in patients for whom CTA had already been performed. Where new lesions had been identified at follow-up, the imaging was retroactively reviewed to assess if they were present on the index imaging. Results Two hundred seven consecutive patients were reviewed. Significant (> 50%) intracranial atherosclerotic disease was present on MRA in 18 patients (8.7%). This was a new finding in 11 patients. Five had initial CTA where the atherosclerosis was not detected. All 5 of these cases were located in the posterior cerebral arteries. Incidental aneurysms were seen in 14 (6.7%); 12 were a new finding at time of MRI. Conclusion The MRA sequence provides additional value by increasing the detection of clinically important intracranial atherosclerotic disease which may inform management in patients with minor stroke and TIA.

Background Inflammation driven by pro-inflammatory cytokines is a new therapeutic target in coronary disease. Few data exist on the association of key upstream cytokines and post-stroke recurrence. In a prospective cohort study, we investigated the association between pivotal cytokines, high-sensitivity C-reactive protein (hsCRP) and one-year outcomes. Methods BIO-STROKETIA is a multi-center prospective cohort study of non-severe ischemic stroke (modified Rankin score ≤ 3) and transient ischemic attack. Controls were patients with transient symptoms attending transient ischemic attack clinics with non-ischemic final diagnosis. Exclusion criteria were severe stroke, infection, and other pro-inflammatory disease; hsCRP and cytokines (interleukin (IL) 6, IL-1β, IL-8, IL-10, IL-12, interferon-γ (IFN-γ), tumor-necrosis factor-α (TNF-α)) were measured. The primary outcome was one-year recurrent stroke/coronary events (fatal and non-fatal). Results In this study, 680 patients (439 stroke, 241 transient ischemic attack) and 68 controls were included. IL-6, IL-1β, IL-8, IFN-γ, TNF-α, and hsCRP were higher in stroke/transient ischemic attack cases (p ≤ 0.01 for all). On multivariable Cox regression, IL-6, IL-8, and hsCRP independently predicted one-year recurrent vascular events (adjusted hazard ratios (aHR) per-quartile increase IL-6 1.31, confidence interval (CI) 1.02–1.68, p = 0.03; IL-8 1.47, CI 1.15–1.89, p = 0.002; hsCRP 1.28, CI 1.01–1.62, p = 0.04). IL-6 (aHR 1.98, CI 1.26–3.14, p = 0.003) and hsCRP (aHR 1.81, CI 1.20–2.74, p = 0.005) independently predicted one-year fatality. IL-6 and hsCRP (adjusted odds ratio per-unit increase 1.02, CI 1.01–1.04) predicted poor functional outcome, with a trend for IL-1β (p = 0.054). Conclusion Baseline inflammatory cytokines independently predicted late recurrence, supporting a rationale for randomized trials of anti-inflammatory agents for prevention after stroke and suggesting that targeted therapy to high-risk patients with high baseline inflammation may be beneficial.

Poster B4 Environmental genomics is a rapidly advancing field that promises to revolutionise the way in which industry conducts biodiversity monitoring. The International Association of Oil and Gas Producers Environmental Genomics Joint Industry Program (JIP) was formed in June 2019 with the aim of facilitating the development and uptake of environmental genomics within the oil and gas industry. Towards this goal, a white paper was produced that summarises the state‐of‐the‐art in environmental genomics research, and the opportunities and limitations of applying environmental genomics within industry. The white paper included a comprehensive literature review, and importantly, involved consultation with professionals from academic, regulatory and industry backgrounds from across the globe that had expertise in environmental genomics applications. While this consultation revealed a consensus that the application of environmental genomics has advanced greatly in a brief period, with demonstrable benefits, there was an acknowledgement that key aspects are still lacking that would allow confident application of genomics approaches within industry. Through the review and consultation process, a range of knowledge gaps and areas requiring further development were identified. To elucidate which of these areas were most critical to the successful application of environmental genomics within industry, the JIP is drafting guidance that describes sampling design considerations, minimum standards for laboratory analyses and approaches to genomics data interpretation. Through the drafting of guidance, the JIP hopes to determine which gaps are most critical, enabling these to be prioritised for targeted research. The guidance will then be updated regularly to capture the latest research outcomes. To access the poster click the link on the right. To read the full paper click here

Background and ObjectivesIn pooled analyses of endarterectomy trials for symptomatic carotid stenosis, several subgroups experienced no net benefit from revascularization. The validated symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score includes stenosis severity and inflammation measured by PET and improves the identification of patients with recurrent stroke compared with lumen-stenosis alone. We investigated whether the SCAIL score improves the identification of recurrent stroke in subgroups with uncertain benefit from revascularization in endarterectomy trials.MethodsWe did an individual-participant data pooled analysis of 3 prospective cohort studies (Dublin Carotid Atherosclerosis Study [DUCASS], 2008–2011; Biomarkers and Imaging of Vulnerable Atherosclerosis in Symptomatic Carotid Artery Disease [BIOVASC], 2014–2018; Barcelona Plaque Study, 2015–2018). Eligible patients had a recent nonsevere (modified Rankin Scale score ≤3) anterior circulation ischemic stroke/TIA and ipsilateral mild carotid stenosis (14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed.ResultsWe included 135 patients. All patients started optimal modern-era medical treatment at admission, and 62 (45.9%) underwent carotid revascularization (36 within the first 14 days and 26 beyond). At 90 days, 18 (13.3%) patients had experienced at least 1 stroke recurrence. The risk of recurrence increased progressively according to the SCAIL score (0.0% in patients scoring 0–1, 15.1% scoring 2–3, and 26.7% scoring 4–5; p = 0.04). The adjusted (age, smoking, hypertension, diabetes, carotid revascularization, antiplatelets and statins) hazard ratio for ipsilateral recurrent stroke per 1-point SCAIL increase was 2.16 (95% CI 1.32–3.53; p = 0.002). A score ≥2 had a sensitivity of 100% for recurrence.DiscussionThe SCAIL score improved the identification of early recurrent stroke in subgroups who did not experience benefit in endarterectomy trials. Randomized trials are needed to test whether a combined stenosis-inflammation strategy will improve selection for carotid revascularization when benefit is currently uncertain.Classification of EvidenceThis study provides Class II evidence that, in patients with recent anterior circulation ischemic stroke who do not benefit from carotid revascularization, the SCAIL score accurately distinguishes those at risk for recurrent ipsilateral ischemic stroke.

Leukoencephalopathy with brain calcifications and cysts (LCC) is a rare cerebral microangiopathy, the cause of which was recently determined to be recessively inherited mutations in the SNORD118 gene. We report the case of a 32-year-old Irish Traveller woman who presented to the emergency department in convulsive status epilepticus with abnormal neuroimaging features characteristic of LCC. Her medical history consisted of epilepsy, intellectual impairment, previous craniotomies for excision of cerebral cysts and resection of a tibial osteogenic sarcoma. Whole exome sequencing identified a previously described homozygous variant, NR_033294.1 n.*5C>G, in the 3' UTR of the SNORD118 gene. Her sister was subsequently found to be homozygous for the same variant but with a significantly milder clinical phenotype consisting of migraine without aura and mild, non-specific, cerebral white matter changes on neuroimaging. Knowledge of the existence of LCC within this population means that targeted genetic testing for this specific mutation should be considered in Irish Traveller patients presenting with the characteristic clinical and radiological features. Given the striking phenotypic variability seen within this family, LCC should also be considered in Irish Traveller patients even in the absence of the complete radiological triad.

This case raises the potential association between cervical arterial dissection and VZV vasculopathy. We advise angiographic imaging of neck vessels when VZV vasculopathy is suspected.

Background Inflammation plays a role in the development of ischaemic cerebrovascular events. High sensitivity C-reactive protein (CRP) is known to predict recurrent events. Little data exists for more upstream serum markers of inflammation. Methods BIO-STROKE and BIO-TIA were multicentre prospective biomarker and imaging studies of patients with non-severe stroke, TIA and controls. Exclusion criteria were malignancy, infection, recent trauma / surgery, recurrent stroke before phlebotomy/MRI. Serum biomarkers analysed included Interleukin (IL) – 6, CRP, IL-1, IL-8, IL10, IL12p70, IFN and TNF.Plasma CRP and IL-6 were measured by mass spectrometry. Additional biomarkers were measured using ELISA. Follow up was performed at 7, 28, 90 days and 1 year. Results 680 patients (439 strokes, 241 TIAs) and 68 controls were included in the analysis. The median age was 70 for cases. Carotid stenosis was present in 23.6% of cases. Median CRP was 3.75mg/L, 2.36mg/l and 1.87mg/L in the stroke, TIA and control groups (p= On multivariate cox regression analysis baseline IL6 and CRP were independent predictors of all cause death at 1 year with a HR of 1.005 (95% CI 1.002-1.007, p On adjusted analysis, when IL6 was analysed as quartiles, there was a strong association with death at 1 year with an OR 1.87 (95% CI 1.19-2.93).CRP, analysed as quartiles, demonstrated an OR for death at 1 year of 1.64 (1.10-2.46). Conclusion IL-6 and CRP may be a useful prognostic factor for the prediction of outcome and death after stroke at 1 year follow up.

Background Acute stroke and its aftermath is the commonest cause of acquired disability amongst community dwelling adults. Analysis of hospital discharge rates over time and the influence of patient age is important and may offer important insights on how best to configure stroke prevention and clinical services. Here, we analyse hospital discharge data for Ireland for 2005-2017. Methods A retrospective review of stroke discharges, with a primary diagnosis of stroke or subarachnoid haemorrhage, was performed. National data on acute hospital discharge from all acute hospitals in Ireland was obtained from the Hospital Inpatient Patient Enquiry (HIPE) database for discharges between 1st January 2005 and 31st December 2017. Results were examined across 4 age groups; 15-49 years, 49 to 64 years, 65 to 80 years and >80 years. Age specific acute stroke hospital discharge rates were calculated using Irish population census data. Results There has been a steady increase in the incidence of ischaemic stroke in those between 15- 49 years between 2005-2017 (0.08 v 0.18 per 1,000 patient-years). Rates of haemorrhagic stroke remained stable. A similar increase was noted in those aged 50-64 years. There is a small downward trend in the incidence of ischaemic stroke in the 65-80 year age category (4.31 v 3.82 per 1000-patient years), with the biggest decrease in females. Stroke rates in the over 80s has remained stable. Conclusion Better understanding is needed of the risk factors underlying this worrying trend. Clinical service providers will need to adapt to better deal with the challenges specific to stroke at younger age.

Background and Purpose— Plaque inflammation contributes to stroke and coronary events. 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18 F-FDG uptake and early recurrent stroke. Methods— We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18 F-FDG PET/computed tomography angiography, 18 F-FDG uptake was expressed as maximum standardized uptake value (SUV max ) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUV max with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results— In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUV max was 2.2 (CI, 1.1–4.5; P =0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1–4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98–5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUV max was higher in patients with all recurrence ( P P =0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41–3.39; P P =0.008). Recurrent stroke risk increased across SUV max quartiles (log-rank P =0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59–0.78) and for post-PET recurrence was 0.80 (CI, 0.64–0.96). Conclusions— Plaque inflammation-related 18 F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18 F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

Patients with TIA and minor stroke commonly undergo CT and CTA in the emergency department with subsequent MRI with MRA for further workup. The purpose of this study was to review outpatient MRIs for TIA/stroke patients to assess the additional benefit, if any, of the MRA sequence in the detection of intracranial atherosclerotic disease in patients for whom CTA had already been performed.The radiology reports of outpatient MRIs of the brain for TIA/minor stroke patients were retrospectively reviewed via the hospital PACS system. Following this, the imaging report from the patient's initial presentation to the emergency department was reviewed. This index imaging and subsequent MRI were compared to assess the incidence of new vascular findings detected on the MRA sequence in patients for whom CTA had already been performed. Where new lesions had been identified at follow-up, the imaging was retroactively reviewed to assess if they were present on the index imaging.Two hundred seven consecutive patients were reviewed. Significant ( 50%) intracranial atherosclerotic disease was present on MRA in 18 patients (8.7%). This was a new finding in 11 patients. Five had initial CTA where the atherosclerosis was not detected. All 5 of these cases were located in the posterior cerebral arteries. Incidental aneurysms were seen in 14 (6.7%); 12 were a new finding at time of MRI.The MRA sequence provides additional value by increasing the detection of clinically important intracranial atherosclerotic disease which may inform management in patients with minor stroke and TIA.

The International Association of Oil and Gas Producers (IOGP) Environmental Genomics Joint Industry Program (JIP) was formed in June 2019. The aim of the JIP is to facilitate the development of guidelines for the application of environmental genomics to support environmental management activities in the oil and gas industry. Towards this goal, a white paper summarizing the state-of-the-art in environmental genomics research and how it may be used to advance technology development opportunities for the oil and gas industry was drafted. More specifically, a series of applications and focus areas of primary interest to oil and gas companies were covered including: baseline assessments; detection of key species; rapid assessment of invasive species; population status and dynamics; monitoring of environmental effects of oil and gas activities; remediation and restoration; sampling design; data analysis and interpretation; community representation; species abundance, distribution and viability; and real-time on-site measurement and analysis. baseline assessments; detection of key species; rapid assessment of invasive species; population status and dynamics; monitoring of environmental effects of oil and gas activities; remediation and restoration; sampling design; data analysis and interpretation; community representation; species abundance, distribution and viability; and real-time on-site measurement and analysis. In addition to the literature review, consultation of professionals from academic, regulatory, and industrial backgrounds with expertise on these topics was conducted. While there was a consensus that the application of environmental genomics has advanced greatly in a short period of time with demonstrable benefit potential, there was acknowledgement that key aspects of best management practices are still lacking. Furthermore, while the majority of regulators interviewed were aware to varying degrees of the methodological limitations which restrict the present use of environmental genomics in regulatory affairs, it transpired that there is considerable appetite and capacity amongst the regulatory community to engage in collaborative research initiatives with the oil and gas industry and academia. Through these academic, regulatory, and industrial consultation, specific environmental genomics study areas and applications requiring further development and refinement were identified. These include: methodological standardization, persistence and dispersal of eDNA; eDNA data integration with various other data types; improvement of reference databases; and refinement of molecular indices. methodological standardization, persistence and dispersal of eDNA; eDNA data integration with various other data types; improvement of reference databases; and refinement of molecular indices. Based on the above and considering the most efficient path to greater regulatory uptake for environmental genomic approaches for the oil and gas industry, the JIP’s recommendation is to pursue a Common-Garden Experiment. Such experiment should seek the involvement and ultimately endorsement from the Regulators marking the path towards wider regulatory acceptance and uptake of eDNA-based approaches.

Background and ObjectivesTo determine whether carotid plaque inflammation identified by 18F-fluorodeoxyglucose (18FDG)-PET is associated with late (5-year) recurrent stroke.MethodsWe did an individual-participant data pooled analysis of 3 prospective studies with near-identical study methods. Eligible patients had recent nonsevere (modified Rankin Scale score ≤3) ischemic stroke/TIA and ipsilateral carotid stenosis (50%–99%). Participants underwent carotid 18FDG-PET/CT angiography ≤14 days after recruitment. 18FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice of symptomatic plaque. We calculated the previously validated Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, which incorporates a measure of stenosis severity and 18FDG uptake. The primary outcome was 5-year recurrent ipsilateral ischemic stroke after PET imaging.ResultsOf 183 eligible patients, 181 patients completed follow-up (98.9%). The median duration of follow-up was 4.9 years (interquartile range 3.3–6.4 years, cumulative follow-up period 901.8 patient-years). After PET imaging, 17 patients had a recurrent ipsilateral ischemic strokes at 5 years (recurrence rate 9.4%, 95% confidence interval [CI] 5.6%–14.6%). Baseline plaque SUVmax independently predicted 5-year ipsilateral recurrent stroke after adjustment for age, sex, carotid revascularization, stenosis severity, NIH Stroke Scale score, and diabetes mellitus (adjusted hazard ratio [HR] 1.98, 95% CI 1.10–3.56, p = 0.02 per 1–g/mL increase in SUVmax). On multivariable Cox regression, SCAIL score predicted 5-year ipsilateral stroke (adjusted HR 2.73 per 1-point increase, 95% CI 1.52–4.90, p = 0.001).DiscussionPlaque inflammation–related 18FDG uptake improved identification of 5-year recurrent ipsilateral ischemic stroke. Addition of plaque inflammation to current selection strategies may target patients most likely to have late and early benefit from carotid revascularization.Classification of EvidenceThis study provides Class I evidence that in individuals with recent ischemic stroke/TIA and ipsilateral carotid stenosis, carotid plaque inflammation–related 18FDG uptake on PET/CT angiography was associated with 5-year recurrent ipsilateral stroke.

Introduction: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25–30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. Methods: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. Results: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1β, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01–1.05], p = 0.003). Conclusion: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

Background and Purpose— In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18 F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18 F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods— We derived the score in a prospective cohort study of recent (18 F-fluorodeoxyglucose standardized uptake values (SUV max max 2–2.99 g/mL, 1 point; SUV max 3–3.99 g/mL, 2 points; SUV max ≥4 g/mL, 3 points) and stenosis ( Results— In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score ( P =0.002, C statistic 0.71 [95% CI, 0.56–0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2–4.5, P =0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9–5], P P =0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46–0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66–0.97], P =0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39–5.39], P =0.004). Conclusions— The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

Protocadherin 19 (PCDH19)-related epilepsy (OMIM 300088) is a distinctive clinical syndrome limited to females. We describe a 17-year-old girl who presented to a regional epilepsy clinic with a history of recurrent febrile seizures in infancy. Genetic analysis of the PCDH19 gene revealed a novel heterozygous mutation within a highly conserved region of the gene. Patients with PCDH19 mutations present with clusters of seizures associated with fever. While fever-induced seizures are common to children with PCDH19 and SCN1A mutations, there are certain clinical features that distinguish these genetic syndromes from each other. PCDH19 mutation demonstrates an unusual form of transmission such that only heterozygous females develop the phenotype. De novo mutations account for most cases although the inheritance is sometimes familial patterns of inheritance. Hemizygous males are typically unaffected. Identification of the mutation provides patients and their families with an explanation for their clinical presentation, important prognostic information and an opportunity for genetic counselling.

Background and Purpose- Plaque inflammation contributes to stroke and coronary events.

Background Few studies have directly compared stroke recurrence rates after stroke and transient ischemic attack, and the risk factors underlying early recurrence are poorly understood. We aimed to investigate risk factors for recurrent stroke after first stroke and transient ischemic attack in a population-based study. Methods The North Dublin Population Stroke Study applied multiple overlapping hot and cold pursuit methods, to ascertain hospital- and community-treated stroke and transient ischemic attack patients over a 12-month period. Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and 90 days. Results A total of 584 patients met eligibility criteria (172 transient ischemic attack, 412 stroke). More transient ischemic attack than stroke patients presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p = 0.0002). Recurrent stroke was more common after transient ischemic attack than index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90 days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also associated with delay seeking medical attention after the index event (OR 3.2, p = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p = 0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On multivariable analysis, transient ischemic attack as index event (adjusted OR 2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day recurrent stroke. Conclusion A combination of pathophysiological and behavioral factors was associated with early stroke recurrence risk. Improved public awareness to reduce delays to self-referral for transient ischemic attack symptoms is needed.

To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p0.01) and low CSF-Aβ (p0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p0.05). In a similar logistic regression model, parietal and occipital (p0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p0.05) and occipital PVWMH and elevated CSF-phospho-tau (p0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

PurposeInflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke.ParticipantsThe Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%–99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts.Findings to dateWe have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date.Future plansThe primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic ‘culprit’ carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.

BACKGROUND: Stroke patients are at increased risk of falls and fractures. The aim of this study was to determine the rate, predictors and consequences of falls within 2 years after stroke in a prospective population-based study in North Dublin, Ireland. DESIGN: Prospective population-based cohort study. SUBJECTS: 567 adults aged >18 years from the North Dublin Population Stroke Study. METHODS: Participants were enrolled from an Irish urban population of 294,592 individuals, according to recommended criteria. Patients were followed for 2 years. Outcome measures included death, modified Rankin Scale (mRS), fall and fracture rate. RESULTS: At 2 years, 23.5% (124/522) had fallen at least once since their stroke, 14.2% (74/522) had 2 or more falls and 5.4% (28/522) had a fracture. Of 332 survivors at 2 years, 107 (32.2%) had fallen, of whom 60.7% (65/107) had 2 or more falls and 23.4% (25/107) had fractured. In a multivariable model controlling for age and gender, independent risk factors for falling within the first 2 years of stroke included use of alpha-blocker medications for treatment of hypertension (P = 0.02). When mobility measured at Day 90 was included in the model, patients who were mobility impaired (mRS 2-3) were at the highest risk of falling within 2 years of stroke [odds ratio (OR) 2.30, P = 0.003] and those functionally dependent (mRS 4-5) displayed intermediate risk (OR 2.02, P = 0.03) when compared with independently mobile patients. CONCLUSION: Greater attention to falls risk, fall prevention strategies and bone health in the stroke population are required. Language: en

Background and Purpose— Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population–based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). Methods— Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. Results— Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype ( P P =0.005) and prior stroke (adjusted hazard ratio, 2.92; P =0.01) were independent predictors of 2-year recurrence in 28-day survivors. Conclusions— Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.

Few population-based studies have assessed lipid adherence to international guidelines for primary and secondary prevention in stroke/transient ischaemic attack (TIA) patients. This study aims to evaluate adherence to lipid-lowering therapy (LLT) guidelines amongst patients with ischaemic stroke/TIA. Using hot and cold pursuit methods from multiple hospital/community sources, all stroke and TIA cases in North Dublin City were prospectively ascertained over a 1-year period. Adherence to National Cholesterol Education Programme (NCEP) III guidelines, before and after index ischaemic stroke/TIA, was assessed. Amongst 616 patients (428 ischaemic stroke, 188 TIA), total cholesterol was measured following the qualifying event in 76.5% (471/616) and low-density lipoprotein (LDL) in 60.1% (370/616). At initial stroke/TIA presentation, 54.1% (200/370) met NCEP III LDL goals. Compliance was associated with prior stroke (odds ratio [OR] 2.19, p = 0.02), diabetes (OR 1.91, p = 0.04), hypertension (OR 1.57, p = 0.03), atrial fibrillation (OR 1.78, p = 0.01), pre-event LLT (OR 2.85, p

To describe and evaluate a novel technical development to improve detection of intracranial vessel occlusions using multiphase CT angiography (MPCTA). The institutional ethics committee approved the study. Fifty patients (30 consecutive distal (M2 or smaller) anterior circulation occlusions, ten M1 occlusions, ten cases without occlusion) presenting with suspected AIS who underwent MPCTA were included. Post-processing of MPCTA studies created “subtraction” and “delayed enhancement” (DE) datasets. Initially, non-contrast CT and MPCTA studies for each patient were evaluated. Readers' confidence, speed and sensitivity of detection of intracranial vessel occlusions were recorded. After an interval of at least 4 weeks, readers were provided with post-processed images and studies were re-evaluated. While the sensitivity of detection of intracranial vessel occlusions was equal for both conventional MPCTA and subMPCTA, the mean time taken to identify a vessel occlusion decreased by 64 % using subMPCTA (16 s vs. 45 s with conventional MPCTA) (p

Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18 fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUV max ) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUV ROImax ); (3) averaged mean SUV across 10 ROIs (SUV mean ). Results: Sixty-one patients were included. Plaque inflammatory FDG SUV max was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol ( p = 0.009), and triglycerides ( p = 0.01), and with lower high-density lipoprotein (HDL) ( p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUV mean (Spearman rho 0.44, p = 0.009), SUV ROImax (rho 0.33, p = 0.01), and SUV max (rho 0.35, p = 0.06). Total cholesterol was associated with SUV mean (rho 0.33, p = 0.009), with trends for SUV max (rho 0.24, p = 0.059) and SUV ROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUV max (rho 0.32, p = 0.01) and SUV ROImax (rho 0.35, p = 0.005). HDL was associated with lower SUV max (rho −0.37, p = 0.004) and SUV ROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL ( p = 0.008) and total cholesterol ( p = 0.04) were independently associated with SUV max . Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.

We describe a unique patient who experienced a progressive autoimmune coma from age 14 to 17. The patient awoke after treatment with immunosuppressant medication. Although alertness, verbalization, and mobilization markedly improved, the patient reported persistent cognitive difficulties. Neuropsychological assessment from age 21 showed impairments in selective attention, distractibility, and memory. Conversely, higher-order executive functions were preserved. Electrophysiological analysis also identified abnormal neural signatures of selective attention. Eighteen months after the neuropsychological assessment, voxel-based morphometry revealed reduced white matter in the medulla compared to controls. The findings are discussed in terms of the impact of brainstem encephalopathy on cognitive mechanisms.

Background and Purpose— The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. Methods— Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005–November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity ( Results— Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5–1.79; first-ever stroke), 0.28 (95% CI, 0.22–0.35; recurrent stroke), and 0.45 (95% CI, 0.37–0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; P Conclusions— Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.

Background and Purpose— Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). Methods— We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. Results— One hundred seventy-five patients had atrial fibrillation–associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P =0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P P =0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=−0.65; P P =0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P =0.04). Conclusions— In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.

Objective: In the North Dublin Population Stroke Study, we investigated the risk of recurrent stroke within the 14-day time window recommended for endarterectomy. Methods: In a population-based prospective cohort study, all ischemic stroke patients were identified over 1 year and categorized into those with (CS-positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (≥50% lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and 7 and 14 days. Results: Of 365 ischemic stroke patients with carotid imaging, 51 were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral carotid occlusion, or intracranial stenosis, leaving 314 included for analysis (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS-positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset ( p = 0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients ( p = 0.01) by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients by 14 days ( p = 0.02). On multivariable Cox regression analysis, CS was the only independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1, 95% confidence interval [CI] 1.6–837.5, p = 0.03), and 7 days (HR 9.1, 1.1–79.2, p = 0.05), with a trend at 14 days (HR 4.6, 0.9–22.8, p = 0.06). Conclusions: Although only a minority of patients with symptomatic CS had a recurrent stroke within 14 days, early recurrent stroke risk was high, particularly within the first 72 hours. Earlier carotid revascularization or improved acute medical treatment may reduce recurrence in this high-risk group.

Background and Purpose— Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study. Methods— A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied. Results— In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P P =0.004), large artery atherosclerosis (relative increase 44.1%; P =0.00006), small artery occlusion (relative increase 27.3%; P =0.00006), and other causes (relative increase 91.7%; P =0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P =0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P =0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P =0.2). Agreement between systems ranged from good (κ=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (κ=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases. Conclusion— Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.

Background and Purpose— Transient ischemic attack (TIA) etiologic data and the ABCD 2 score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD 2 score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA. Methods— Patients with TIA in the North Dublin city population (N=294 529) were ascertained by using overlapping hospital and community sources. The relations between individual ABCD 2 items, carotid stenosis, atrial fibrillation, and early stroke were examined. Results— In confirmed TIA cases (n=443), carotid stenosis predicted 90-day stroke (hazard ratio=2.56; 95% CI, 1.27 to 5.15, P =0.003). Stroke risk rose with increasing grade of carotid stenosis, ranging from 5.4% (95% CI, 3.3% to 8.7%) with P =0.002). In confirmed TIA cases (n=443), the ABCD 2 score performed no better than chance for prediction of 90-day stroke ( c -statistic=0.55; 95% CI, 0.45 to 0.64), largely related to the 24.2% (8/33) of patients who experienced a recurrence and had low ABCD 2 scores (0–3). However, in nonspecialist-suspected TIA cases (n=700), the predictive utility improved for stroke at 28 ( c -statistic=0.61; 95% CI, 0.50 to 0.72) and 90 ( c -statistic=0.61; 95% CI, 0.52 to 0.71) days. Conclusions— In a population-based TIA cohort, significant predictive information was provided by carotid stenosis. The ABCD 2 score had predictive utility in patients with TIA suspected by nonspecialists. Low scores occurred in several patients with stroke recurrences, suggesting that caution is needed before using the score in isolation.

Background and Purpose— Transient ischemic attack (TIA) diagnosis is frequently difficult in clinical practice. Noncerebrovascular symptoms are often misclassified as TIA by nonspecialist physicians. Clinical prediction rules such as ABCD 2 improve the identification of patients with TIA at high risk of early stroke. We hypothesized that the ABCD 2 score may partly improve risk stratification due to improved discrimination of true TIA and minor ischemic stroke (MIS) from noncerebrovascular events. Methods— Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD 2 score. Results— Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD 2 score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P 2 score discriminated well between noncerebrovascular and cerebrovascular events—TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)—from noncerebrovascular events. Of ABCD 2 items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups. Conclusion— The ABCD 2 score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.

Alzheimer Disease (AD) is the most common primary cause of dementia with a burgeoning epidemic as life expectancy and general medical care improve worldwide. Recent data from pathologic studies has shown that the cooccurrence of other neurodegenerative and vascular pathologies is in fact the rule rather than the exception. In late onset AD, cerebral small vessel disease (SVD) is almost invariably co-existent to a greater or lesser extent and is known to promote cognitive deterioration. Previous observational studies and clinical trials have largely sought to divide dementia based on predominant neurodegenerative or vascular mechanisms. Given the high degree of overlap, findings from such studies may be difficult to interpret and apply to population cohorts. Additionally opportunities may be lost for uncovering novel interventions that target interactions between co-existent vascular and neurodegenerative pathologies. In the current review, we consider potential pathophysiologic mechanisms through which SVD may be associated with and promote AD pathology. In particular we explore shared environmental and genetic associations and how these may converge via neuroinflammatory pathways potentially providing novel therapeutic targets. SVD has heterogenous manifestations on cerebral imaging and at pathology. We discuss how studying SVD topography may enable us to better identify those at risk for more rapid cognitive decline and improve future clinical trial design.

Background and Purpose— Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. Methods— Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis ≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. Results— Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade ≥3; 91.7% versus 37.5%; P =0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P =0.004), neovascularization (OPS grade ≥2; 83.3% versus 43.8%; P =0.04), and low plaque fibrous content (OPS grade P =0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%–98.8%) in patients with extensive plaque macrophage infiltration (OPS grade ≥3) compared with 22.2% (confidence interval, 3.5%–83.4%) in those with OPS grade P =0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or P =0.04). Conclusions— Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.

Introduction Accurate health economics data is essential for service planning and clinical guideline development. Stroke associated with atrial fibrillation (AF) is characteristically more severe and disabling than non-AF stroke. Few data exist on the economic impact of AF-stroke compared to non-AF-stroke in population-based samples. Methods The North Dublin Population Stroke Study is a population-based prospective study of incident stroke in Dublin, Ireland. Both direct (healthcare-related) and indirect costs were calculated over a 2-year post-stroke period for individual patients, using data for survival and disability, discharge destination, outpatient and family practitioner visits, community supports, and ongoing treatment. Acute inpatient care was costed using the casemix approach, measuring the resource use per hospitalization (index stroke plus post-stroke admissions). Length of stay was used to cost rehabilitation and nursing home admissions. Indirect costs of illness were calculated using in-hospital length of stay to determine loss of productivity. Total costs were compared for AF-stroke and non-AF stroke, calculated at 2007 prices and converted to US$ (2007 rates). Results Of 568 ischemic and hemorrhagic incident stroke patients, 31% (177) had AF-associated stroke. 2-year fatality was higher in AF-stroke patients (50.3% versus 35.1%, p=0.001). Total 2-year median cost was $34,982 for AF-stroke patients (25-75% IQR $14,213-$88,283) compared to median cost of $17,736 (25-75% IQR $10,803-45,838] in non-AF stroke patients (p Conclusion In this population study, AF-associated stroke was associated with substantially higher costs for hospitalisation and community support after discharge. With ageing populations and increasing stroke burden, AF-stroke is likely to account for an increasing proportion of overall cost to health services.

Background Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intra-plaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18 F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) we investigated the relationship between inflammation-related FDG uptake and stroke recurrence. Methods Consecutive patients with a recent (median 6.5 days [IQR 4-8]) stroke, TIA, or retinal embolism and ipsilateral carotid stenosis ( ≥50%) were included. FDG uptake was quantified as mean standardised uptake values (SUV, g/ml). Patients were followed prospectively for stroke recurrence. Results 60 patients were included (25 stroke, 29 TIA, 6 retinal embolism). 22% (13/60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV 1.85 [SD 0.44] vs. 1.58 [SD 0.32] g/ml, p=0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14g/ml threshold were 80% (CI 41.8-99.2%) versus 22.9% (CI 12.3-40.3%) with SUV ≤2.14g/ml (log-rank p Conclusion In recently-symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularisation or intensive medical treatment.

Objective: Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. Methods: Consecutive patients with a recent (median, 6.5 days; interquartile range, 4–8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. Results: Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85g/ml; standard deviation [SD], 0.44 vs 1.58g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14g/ml threshold were 80% (95% confidence interval [CI], 41.8–99.2) versus 22.9% (95% CI, 12.3–40.3) with SUV ≤2.14g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50–69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3–28.8; p = 0.02). Interpretation: In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment. ANN NEUROL 2012

Background and Purpose— Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. Methods— A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (≤72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. Results— Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (≤72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03–0.54 at 7 days; OR, 0.19; CI, 0.07–0.48 at 90 days; OR, 0.26; CI, 0.12–0.55 at 1 year; P ≤0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00–0.33; P =0.003 at 7 days; OR, 0.23; CI, 0.09–0.58; P =0.002 at 90 days; OR, 0.48; CI, 0.23–1.01; P =0.05 at 1 year). Conclusions— Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed.

Background: Prospective population-based studies are important to accurately determine the incidence and characteristics of stroke associated with atrial fibrillation (AF), while avoiding selection bias which may complicate hospital-based studies. Methods: We investigated AF-associated stroke within the North Dublin Population Stroke Study, a prospective cohort study of stroke/transient ischaemic attack in 294,592 individuals, according to recommended criteria for rigorous stroke epidemiological studies. Results: Of 568 stroke patients ascertained in the first year, 31.2% (177/568) were associated with AF (90.4%, i.e. 160/177 ischaemic infarcts). The crude incidence rate of all AF-associated stroke was 60/100,000 person-years (95% CI = 52–70). Prior stroke was almost twice as common in AF compared to non-AF groups (21.9 vs. 12.8%, p = 0.01). The frequency of AF progressively increased across ischaemic stroke patients stratified by increasing stroke severity (NIHSS 0–4, 29.7%; 5–9, 38.1%; 10–14, 43.8%; ≥15, 53.3%, p < 0.0001). The 90-day trajectory of recovery of AF-associated stroke was identical to that of non-AF stroke, but Rankin scores in AF stroke remained higher at 7, 28 and 90 days (p < 0.001 for all). Discussion: AF-associated stroke occurred in one third of all patients and was associated with a distinct profile of recurrent, severe and disabling stroke. Targeted strategies to increase anticoagulation rates may provide a substantial benefit to prevent severe disabling stroke at a population level.