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Background and Objectives: In 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., Methods: We 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 (<50%); ipsilateral moderate carotid stenosis (50%-69%) plus at least 1 of female sex, age <65 years, diabetes mellitus, TIA, or delay >14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18 F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed., Results: We 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., Discussion: The 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 Evidence: This 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., (© 2022 American Academy of Neurology.)

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Background:  The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown., Methods:  This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50-99%) carotid stenosis patients. One-hour transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES+ve or MES-ve., Results:  Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the "early phase" (≤4 weeks) and 37 patients in the "late phase" (≥3 months) after transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher ( p  = 0.049) and VWFpp/VWF:Ag ratios lower ( p  = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES-ve subgroups ( p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity ( p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased ( p ≤ 0.048) and VWFpp/VWF:Ag ratios increased ( p  = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p  = 0.035)., Discussion:  VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES-ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke., Competing Interests: S.J.X.M. reports grants from Trinity College Dublin Innovation Bursary, Meath Foundation, Joint IICN/Merck Serono Fellowship in Neuroscience, The Vascular Neurology Research Foundation, unrestricted educational grant from Bayer HealthCare Ireland, and unrestricted educational grant from Verum Diagnostica, GmbH, outside the submitted work.S.T.L. reports grants from Meath Foundation, the Irish Institute of Clinical Neuroscience (IICN)/Novartis Ireland Fellowship Grant, the Irish Heart Foundation Stroke Prevention Bursary, the Vascular Neurology Research Foundation, Ireland, and unrestricted educational grant funding from Biogen Idec Ireland, outside the submitted work.D.J.H.M. reports grants from the Trinity College Dublin Innovation Bursary, Trinity College Dublin, Ireland, the Meath Foundation, Ireland, Joint IICN/Merck Serono Fellowship in Neuroscience, the Vascular Neurology Research Foundation, Bayer HealthCare Ireland, Verum Diagnostica, GmbH, the Irish Institute of Clinical Neuroscience (IICN)/Novartis Ireland Fellowship Grant, the Irish Heart Foundation Stroke Prevention Bursary, and Biogen Idec Ireland, during the conduct of the study., (Thieme. All rights reserved.)

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation.We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray-Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as 'MES+ve' or 'MES-ve'. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets.Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (25 vs. 30; P  = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P  = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 10 9 /L), neutrophil-platelet (3.3 vs. 2.7%), monocyte-platelet (6.3 vs. 4.55%) and lymphocyte-platelet complexes (2.91 vs. 2.53%) than ' asymptomatic patients with GSM-echodense plaques ' ( P ≤ 0.03).Recently, symptomatic carotid stenosis patients with 'GSM-echodense plaques' have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

Background: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy., Methods: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100 ® and 'low shear stress' with VerifyNow ® and Multiplate ® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve., Results: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100 ® , but not on the VerifyNow ® or Multiplate ® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100 ® (28.6%) vs. VerifyNow ® (9.5%; P = 0.049), but not Multiplate ® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup., Discussion: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100 ® , likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

Introduction:  Cerebral micro-embolic signals (MES) predict risk of stroke in carotid stenosis patients. However, MES-negative 'recently symptomatic patients' also have a higher stroke risk than 'asymptomatic patients'. Differences in platelet activation status may contribute to this disparity in risk., Methods:  This prospective, observational study assessed platelet biomarkers and their relationship with MES in asymptomatic versus symptomatic moderate (≥50-69%) or severe (≥70-99%) carotid stenosis patients. Full blood count parameters were measured and whole-blood flow cytometry was used to quantify platelet surface CD62P and CD63 expression and leucocyte-platelet complex formation. Bilateral simultaneous transcranial Doppler ultrasound of the middle cerebral arteries classified patients as 'MES positive' or 'MES negative'., Results:  Data from 34 asymptomatic patients were compared with those from 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 of these symptomatic patients in the 'late phase' (≥ 3 months) after transient ischaemic attack/ischaemic stroke. There were no differences in %CD62P or %CD63 expression between early or late symptomatic and asymptomatic patients overall ( p  > 0.05). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients (2.8 vs. 2.16%; p  < 0.001). MES were more commonly observed in early symptomatic (31.4%; p  = 0.027) but not in late symptomatic (6.7%; p  = 0.996) versus asymptomatic patients (7.1%). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic MES-negative patients (2.7 vs. 2.17%; p  = 0.02)., Conclusion: These data add to the evidence that leucocyte-platelet complex formation/platelet activation is increased in recently symptomatic versus asymptomatic patients, and may contribute to the pathogenesis of first and subsequent strokes in carotid stenosis patients, including those who are MES negative., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Understanding the experiences of fallers after stroke could inform falls-prevention interventions, which have not yet shown effectiveness in this population. The aim of this study was to explore the experience of recurrent fallers post-stroke in relation to recovery and living with falls., Methods: Participants who had more than one fall in the first year after stroke were identified from a prospective cohort study. The methods of grounded theory informed data collection and analysis. Semi-structured interviews were conducted, audio-recorded and transcribed. Coding was conducted and categories were developed inductively., Results: Nine stroke survivors aged 53-85 were interviewed 18-22 months post-discharge. Participants had experienced between 2 and 9 falls and one participant suffered a fracture. Three inter-linked categories were identified: (i) Judging the importance of falls by exploring cause and consequence, (ii) getting back up, and (iii) being careful., Conclusions: Stroke survivors' assessment of their own falls-risk and their individual priorities contribute to their decisions around activity participation. "Being careful" could be described as a form of self-managing falls-risk. The inclusion of self-management principles, peer-educators, and education to rise from the floor in falls-management programmes warrants investigation. Not all falls were considered equally important by participants. This could be considered when defining falls-related outcomes. Implications for Rehabilitation Healthcare professionals may be able to offer an increased sense of control to stroke survivors through education about how to avoid particular causes and consequences of falls. Falls-related advice should be specific, relevant to the individual, and respectful of their sense of identity. Being able to rise from the floor appears to be important for coping with falls and falls-risk. Professionals should be cognisant of the potential differences of opinion between stroke survivors and their families around management of falls-risk.

Introduction: Falls are common post-stroke adverse events. This study aimed to describe the first-year falls incidence, circumstances and consequences among persons discharged home after stroke in Ireland, and to examine the association between potential risk factors and recurrent falls., Patients and Methods: Patients with acute stroke and planned home-discharge were recruited consecutively from five hospitals. Variables recorded pre-discharge included: age, stroke severity, co-morbidities, fall history, prescribed medications, hemi-neglect, cognition and functional independence (Barthel index). Falls were recorded with monthly diaries, and 6 and 12-month interviews. The association of pre-discharge factors with recurrent falls (>1 fall) was examined using univariable logistic regression., Results: A total of 128 participants (mean age = 68.6, SD = 13.3) were recruited; 110 completed the 12-month follow-up. The first-year falls incidence was 44.5% (95% CI = 35.1-53.6) with 25.6% falling repeatedly (95% CI = 18.5-34.4). Fallers experienced 1-18 falls (median = 2) and five reported fractures; 47% of fallers experienced at least one fall outdoors. Only 10% of recurrent fallers had bone health medication prescribed at discharge. Lower Barthel index scores (<75/100, RR = 4.38, 1.64-11.72) and psychotropic medication prescription (RR = 2.10, 1.13-3.91) were associated with recurrent falls., Discussion: This study presents prospectively collected information about falls circumstances. It was not powered for multivariable analysis of risk factors., Conclusion: One-quarter of stroke survivors discharged to the community fall repeatedly and mostly indoors in the first year. Specific attention may be required for individuals with poor functional independence or those on psychotropic medication. Future falls-management research in this population should explore falls in younger individuals, outdoor as well as indoor falls and post-stroke bone health status.

Introduction: Falls are common post-stroke events but their relationship with healthcare costs is unclear. The aim of this study was to examine the relationship between healthcare costs in the first year after stroke and falls among survivors discharged to the community., Patients and Methods: Survivors of acute stroke with planned home discharges from five large hospitals in Ireland were recruited. Falls and healthcare utilisation data were recorded using inpatient records, monthly calendars and post-discharge interviews. Cost of stroke was estimated for each participant from hospital admission for one year. The association of fall-status with overall cost was tested with multivariable linear regression analysis adjusting for pre-stroke function, stroke severity, age and living situation., Results: A total of 109 stroke survivors with complete follow-up data (mean age = 68.5 years (SD = 13.5 years)) were included. Fifty-three participants (49%) fell following stroke, of whom 28 (26%) had recurrent falls. Estimated mean total healthcare cost was €20,244 (SD=€23,456). The experience of one fall and recurrent falls was independently associated with higher costs of care (p = 0.02 and p < 0.01, respectively)., Discussion: The observed relationship between falls and cost is likely to be underestimated as aids and adaptions, productivity losses, and nursing home care were not included., Conclusion: This study points at differences across fall-status in several healthcare costs categories, namely the index admission, secondary/tertiary care (including inpatient re-admissions) and allied healthcare. Future research could compare the cost-effectiveness of inpatient versus community-based fall-prevention after stroke. Further studies are also required to inform post-stroke bone-health management and fracture-risk reduction.

Background: several multivariable models have been derived to predict post-stroke falls. These require validation before integration into clinical practice. The aim of this study was to externally validate two prediction models for recurrent falls in the first year post-stroke using an Irish prospective cohort study., Methodology: stroke patients with planned home-discharges from five hospitals were recruited. Falls were recorded with monthly diaries and interviews 6 and 12 months post-discharge. Predictors for falls included in two risk-prediction models were assessed at discharge. Participants were classified into risk groups using these models. Model 1, incorporating inpatient falls history and balance, had a 6-month outcome. Model 2, incorporating inpatient near-falls history and upper limb function, had a 12-month outcome. Measures of calibration, discrimination (area under the curve (AUC)) and clinical utility (sensitivity/specificity) were calculated., Results: 128 participants (mean age = 68.6 years, SD = 13.3) were recruited. The fall status of 117 and 110 participants was available at 6 and 12 months, respectively. Seventeen and 28 participants experienced recurrent falls by these respective time points. Model 1 achieved an AUC = 0.56 (95% CI 0.46-0.67), sensitivity = 18.8% and specificity = 93.6%. Model 2 achieved AUC = 0.55 (95% CI 0.44-0.66), sensitivity = 51.9% and specificity = 58.7%. Model 1 showed no significant difference between predicted and observed events (risk ratio (RR) = 0.87, 95% CI 0.16-4.62). In contrast, model 2 significantly over-predicted fall events in the validation cohort (RR = 1.61, 95% CI 1.04-2.48)., Conclusions: both models showed poor discrimination for predicting recurrent falls. A further large prospective cohort study would be required to derive a clinically useful falls-risk prediction model for a similar population., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Introduction: The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients., Methods: Consecutive eligible patients with ≥50% asymptomatic or recently symptomatic carotid stenosis (≤4weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the 'late' phase (≥3months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES +ve or MES -ve., Results: 31 patients with ≥50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of 'high on-treatment platelet reactivity' (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in 'symptomatic post-intervention' than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p=0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p=0.017), including those on aspirin monotherapy (p=0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES +ve or MES -ve patients., Discussion: Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Both psychological distress and fatigue are common post stroke. Although there is recognition that the phenomena are related, the nature of the relationship is unclear.Cross-sectional study of 98 independently functioning participants within 2 years of stroke. Significant relationships were observed between fatigue and general anxiety, health-related anxiety and stroke-specific anxiety (r range from .31 to .37). In the final regression model, depression, pain and stroke-specific anxiety were significant, accounting for 32 per cent of the variance in fatigue scores (p < .001). The findings provide insight into the importance of anxiety-related factors post stroke, their relevance to our understanding of post-stroke fatigue and their implications for post-stroke intervention., (© The Author(s) 2015.)

Introduction: Hypertension is a recognised risk factor for lacunar stroke. However, their association has been evaluated using static blood pressure (BP) assessment in supine or sitting position alone. We hypothesised that impaired dynamic (orthostatic) BP control may associate with lacunar strokes., Patients and Methods: Consecutive subjects with mitral regurgitation (MR) confirmed, lacunar strokes were compared with two control groups. Firstly "normal", age and sex matched, population controls (1:3 ratio) and then 'at risk' controls matched for age, sex, hypertension history and antihypertensive medication (1:2 ratio). Orthostatic BP control was assessed by active stand tests with continuous, phasic, beat-to-beat BP measurement., Findings: Thirty-six subjects (mean 69.9 years) were compared with 108 controls in group 1 and 72 in group 2. Prevalence of syncope was higher among those with lacunar stroke (cases: 44.4%, group 1: 17.6%, p  = 0.003, group 2: 12.5%, p  = 0.0004, Fisher's exact). Mean baseline systolic BP (SBP) was significantly higher in cases (cases: 150 mm Hg, group 1: 140 mm Hg, p  = 0.03, group 2: 143 mm Hg, p  = 0.1). Ten seconds after standing, SBP dropped significantly less in cases (cases: -14.1 mm Hg, group 1: -31.4 mm Hg, p  < 0.0005, group 2: -27.3 mm Hg, p  = 0.001, t test). Diastolic BP also fell significantly less in cases. Cases' SBP and DBP recovered to, then persistently overshot baseline levels., Discussion and Conclusion: Subjects with MR-defined lacunar stroke, of likely small vessel aetiology, exhibit orthostatic hypertension compared with population norms., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A previously well 30-year-old woman presented at 17:30 with a sudden onset of dizziness, ataxia and headache. She was initially investigated with a CT scan of the brain and lumbar puncture, which yielded no diagnosis. Subsequent MR scan revealed multiple posterior circulation infarcts, along with a previously undiagnosed Arnold-Chiari 2 malformation with an associated syrinx of her cervical and thoracic spine. The infarct involved one of the herniated cerebellar tonsils. Oedema of an infarct in the herniated tonsils caused compression of the medulla at the foramen magnum, with associated neurological symptoms including Lhermitte's phenomenon and headache on valsalva manoeuvre. Owing to these symptoms a surgical decompression was performed. The most likely aetiology of her stroke was determined to be a paradoxical embolus via patent foramen ovale., (2016 BMJ Publishing Group Ltd.)

Aims: The prevalence of focal neurology (FN) as a consequence of syncope is unknown. The aim of the study was to determine its prevalence, risk factors and short-term consequences., Methods: A consecutive sample of syncope-unit attendees during a 9-month period had detailed diagnostic syncope evaluation as per European Cardiac Society guidelines coupled with assessment for FN present during syncope/pre-syncope by screening questionnaire, follow-up interview and neuroimaging (1.5T magnetic resonance imaging [MRI]). All participants were followed up for 24 months. Risk factors for FN were identified by comparing FN cases with syncope controls without FN (3:1 ratio)., Results: Five-hundred and forty consecutively attended for investigation of syncope (n = 401) and pre-syncope (n = 139). Thirty-one (5.7%) had FN events during hypotensive symptoms, mean age 49 years (19-85). The majority of FN cases had vasovagal syncope (VVS); 22 (71%), whereas eight had OH (25.8%) and one (3.2%) had cardiac arrhythmia. Median duration of FN was 15 min (IQR: 34.5). MRI in 28 (90%) was normal and in 3, old cerebral infarction was evident. Risk factors for FN/syncope were frequent syncope (P = 0·008), childhood syncope (P < 0.0005) and delayed diastolic recovery during active stand (P = 0·02). During 24-month follow-up and targeted intervention, no patients developed recurrence of FN., Conclusion: One in 20 patients with syncope/pre-syncope have co-extant FN, which during 24-month follow-up, does not progress to a persistent deficit (>24 h). Awareness of co-occurrence of FN and syncope is important as stroke misdiagnosis results in aggressive anti-hypertensive management and future events may ensue., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed., Methods: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative., Results: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup., Discussion: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Purpose: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown., Methods: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative., Results: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 μg/ml; P < 0.001), late (10.6 μg/ml; P = 0.01) and late post-intervention (10.6 μg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 μg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 μg/ml; P < 0.001) than asymptomatic MES-negative patients., Conclusions: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study., (© 2014 The Author(s) European Journal of Neurology © 2014 EAN.)

Introduction: The prevalence of fatigue following stroke and Transient Ischaemic Attack (TIA) is disputed, with prevalences ranging from 30% to 72% reported. We hypothesized that methods and descriptors used may substantially affect the prevalence reported., Methods: Subjects completed validated assessments of fatigue and sleepiness (the Fatigue Severity Scale [FSS] and Epworth Sleepiness Scale [ESS]) as well as 5-point Likert scores on frequency of symptoms using the 5 statements of fatigue derived from patient interviews., Results: Among the 91 subjects, the mean FSS score was 3.8. FSS score correlated more strongly with the statement "I have a lack of energy" (r=0.470; ρ<0.001; Spearman's rho) than with the statement "I feel physical fatigue" (r=0.349; ρ=0.001). The statement "I have a lack of energy" also produced the highest prevalence of severe symptoms, with 37% agreeing that they had the symptom "often" or "always." Agreement between Likert scales was only fair, the best being that for "I have a lack of energy" and "I feel physical fatigue" (κ=0.50). There was a gender difference in simple expression of fatigue, with the statement "I feel physical fatigue" correlating strongly with FSS score in males (r=0.61; ρ<0.001) but not correlating in females (r=0.039; ρ=0.29). Depending on which definition of fatigue was used, the prevalence of fatigue varied between 13% and 63%. FSS score correlated weakly with ESS score (r=0.287; ρ=0.008). Our data indicate significant variation in the prevalence of fatigue among subjects with stroke and transient ischemic attack depending on the descriptors and methods used to define it., Conclusion: There is a significant difference between the genders in how fatigue is expressed., (Copyright © 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Fatigue affects up to 68% of subjects following stroke. In non-stroke patients, associations are reported between chronic fatigue and both hypertension and hypotension. We hypothesized that, in patients with stroke or transient ischaemic attack (TIA), an association may exist between fatigue and abnormal blood pressure (BP) detected on ambulatory monitoring., Methods: Subjects recruited from a secondary prevention clinic underwent 24-h ambulatory BP monitoring and completed a questionnaire including the Fatigue Severity Scale (FSS)., Results: One hundred subjects were included (51% female, mean age 69 years). Mean FSS was 3.6 and 42 has a FSS >4 indicative of significant fatigue. Mean daytime BP for all subjects was 134/74 (SD 16/11 mmHg). There was no significant difference in mean BP between patients with and those without significant fatigue. Patients with stroke suffered worse fatigue than those with TIA (mean FSS 3.8 vs. 3.0, P = 0.03). Twenty-four subjects were hypertensive (mean 24-h BP >145/90 mmHg), 26 had a lowest daytime diastolic BP (DBP) <50 mmHg and 4 had both. Fifty-four subjects were normotensive and these had a significantly lower mean FSS than either those with hypertension (mean FSS 3.2 vs. 4.2, P = 0.02, t-test) or those with low DBP (mean FSS 3.2 vs. 4.2, P = 0.01, t-test). Hypertensive subjects were more likely to be significantly fatigued [chi(2) 3.8, P = 0.05, OR 3.1 (1.1-8.3)] as were subjects with low daytime DBP [chi(2) 8.4, P = 0.004, OR 4.2 (1.5-11.1)]., Conclusion: In subjects who have suffered a stroke or TIA, fatigue is associated with measures of both hypertension and hypotension on ambulatory monitoring. Patients with stroke suffered worse fatigue than those with TIA.