Abstract Background and aims Intracranial artery calcification (IAC) is common and associated with increased stroke risk. Recent studies have identified two subtypes of intracranial carotid artery calcification (ICAC), intimal and internal elastic lamina (IEL) calcification. We investigated the association between IAC volume and morphology with TOAST stroke subtypes, extracranial carotid stenosis (ECS) and recurrent stroke risk. Methods We included patients with a diagnosis of TIA or ischemic stroke with non-cardioembolic etiology enrolled in the CONVINCE trial, who had baseline CT of sufficient quality. IAC volume was quantified on non-contrast CT using a threshold of 130 HU and categorized in tertiles. ICAC morphology was determined by histologically validated CT-based criteria. Associations with etiology according to TOAST and ≥ 50% ECS were assessed by Kruskal-Wallis, chi-squared tests and logistic regression. IAC volume as a predictor for recurrent stroke was analyzed by Kaplan–Meier analysis and Cox regression adjusted for baseline characteristics. Results In a cohort of 519 patients, IAC was present in 475 (91.5%). Patients with large-artery atherosclerosis (LAA) exhibited larger IAC volumes and more intimal dominant ICAC morphology compared with lacunar and cryptogenic aetiologies groups (table 1). With increasing IAC volume, the prevalence of ≥50% ECS was greater (P < 0.001; table 2). The highest IAC tertile had an increased risk of recurrent stroke compared with the lowest (aHR 2.56, 95% CI 1.12-5.84; figure 1). Conclusions Patients with TIA/ischaemic stroke due to LAA had higher IAC volumes and intimal dominant calcification compared with those with lacunar and cryptogenic aetiologies. Increased intracranial artery calcification burden is associated with risk of recurrent stroke. Conflict of interest Tim Cassidy should also be considered an author. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. Table 1 - belongs to Results Table 2 - belongs to Results Figure 1 - belongs to Conclusions

Abstract Background and aims Clopidogrel, a ‘pro-drug’, requires conversion by the cytochrome P450 enzyme system to its active metabolite. NICE(UK) 2024 guidelines recommend genotyping alone, especially for CYP2C19*2/*3 Loss of Function (LOF) Single Nucleotide Polymorphisms (SNPs), in TIA/ischaemic stroke patients, without assessment of Clopidogrel-High on-Treatment Platelet Reactivity (HTPR) status. Methods A Systematic Review and Meta-Analysis was performed to analyse subgroup data from 12 eligible prospective studies in cerebrovascular disease (CVD) patients on clopidogrel monotherapy/combination therapy, which included clopidogrel-HTPR status and CYP2C19 genotyping. Primary composite outcome: Subsequent ischaemic stroke/TIA/myocardial infarction/vascular death. Outcomes were pooled using a restricted maximum likelihood random-effects model with inverse-variance weighting to calculate Risk Ratios (RR) with 95% confidence intervals (CI). Results Clopidogrel-HTPR status predicted outcomes in 6 studies, Pharmacogenetics profiling alone predicted outcomes in 1 study, both Clopidogrel-HTPR and Pharmacogenetics status predicted outcomes in 1 study, and 4 studies showed that neither Clopidogrel-HTPR or Pharmacogenetics profiling predicted outcomes. All were conducted in China or Japan, and were small-medium in size (N=131-501). Meta-analyses showed a statistically-significant increase in the risk of the primary outcome in CVD patients with vs. without Clopidogrel-HTPR on clopidogrel monotherapy or combination therapy (RR ≥ 1.93; 95%CI: 1.58-2.36), with no statistically-significant increase in risk in patients with vs. those without CYP2C19-LOF SNPs (RR ≥1.36; 95%CI: 0.94-1.98). Conclusions The weight of current evidence supports conducting well-designed prospective studies to formally assess the strategy of combining data from platelet reactivity testing with CYP2C19 genotyping to guide precision-based secondary preventive therapy in CVD patients. Conflict of interest No conflict of interest. Our research work is supported by grant funding from several charities and organisations, including the Meath Foundation; The Adelaide Health Foundation; an Enterprise Ireland Innovation Partnership Programme grant with Acquis BI Technology, Ltd.; the VNRF; and in-kind contributions from Werfen, Spain; Sysmex Ireland-UK; Sinnowa, China; Genomadix Inc., Canada and Acquis BI Technology Ltd.

Abstract Background and aims Patients with CYP2C19 loss-of-function (LOF) Single Nucleotide Polymorphisms (SNPs) may be more likely to exhibit ‘Clopidogrel-High on-Treatment Platelet Reactivity’ (HTPR). Few studies concurrently assessed the influence of CYP2C19/other pharmacogenetic factors on Clopidogrel-HTPR status and outcomes in cerebrovascular disease (CVD) patients. Methods In the prospective Optimal Antiplatelet Therapy in TIA and Ischaemic Stroke-International pilot-observational study, 94 TIA-ischaemic stroke patients underwent centralised pharmacogenetics analysis to classify them as predicted CYP2C19 ‘Poor-Intermediate’, ‘Normal’ or ‘Rapid-Ultrarapid’ Clopidogrel Metabolisers. Analyses for candidate SNPs in RAD18, ASIC2 & CYP2C18, and a pilot Genome Wide Association Study (GWAS) were performed. Clopidogrel-treated patients were categorised into subgroups with/without HTPR at ‘high shear-stress’ (PFA-100® INNOVANCE PFA P2Y [Sysmex-Siemens]), & ‘low shear-stress’ (VerifyNow® PRUTest [Werfen], and PL-12/Aggrestar® ADP [Sinnowa]) assays. Results 29% (N=27) were predicted Poor-Intermediate, 37% (N=35) Normal & 34% (N=32) Rapid-Ultrarapid CYP2C19 Metabolisers. 7/21 (33%) Clopidogrel-treated Poor-Intermediate Metabolisers did not have Clopidogrel-HTPR on PFA-100 or VerifyNow assays; 3/21 (14%) did not exhibit Clopidogrel-HTPR on any of the 3 platforms. There was an association between rs10509646 SNP in the HHEX gene on chromosome 10 (pilot GWAS data) and on-treatment platelet reactivity, with shorter median PFA-100 closure times (P=0.0003), and higher mean P2Y12-Reactivity Units on VerifyNow (P=0.005) with homozygous ‘non-wild type’ vs. homozygous ‘wild type (normal)’ HHEX genotypes. Conclusions Almost 1/3 of our CVD population have CYP2C19 LOF SNPs, and up to 33% of these predicted Poor-Intermediate Metabolisers have adequate P2Y12-inhibition on Clopidogrel. Novel SNPs may influence Clopidogrel-HTPR status in CVD patients in Ireland. Conflict of interest No conflict of interest. Prof McCabe's research work is supported by grant funding from several charities and organisations, including the Meath Foundation; The Adelaide Health Foundation; an Enterprise Ireland Innovation Partnership Programme grant with Acquis BI Technology, Ltd.; the VNRF; and in-kind contributions from Werfen, Spain; Sysmex Ireland-UK; Sinnowa, China; Genomadix Inc., Canada and Acquis BI Technology Ltd. *denotes co-first authorship between DS and IN. These data are presented on behalf of the OATS-I Study Research Group, the following members also qualify for authorship on this abstract: Collins DR (4, 14), Ryan DJ (4, 14), McCarthy AJ (1, 3, 4 ), Murphy SM (1, 3), Egan B (15), O’Donnell MJ (16), de Borst GJ (17), Zgaga L (18), Walsh C (18, 19), Kelleher JD (20, 21), Macey C (22), Hennessy M (23, 24): (14) Age-Related Health Care Department, (15) Department of Vascular Surgery, TUH/AMNCH; (16) College of Medicine, Nursing and Health, University of Galway / University Hospital Galway, Galway, Ireland; (17) University Medical Centre Utrecht, Utrecht, Netherlands; (18) Department of Public Health and Primary Care, (19) Department of Biostatistics, (20) Department of Computer Sciences, (21) ADAPT SFI centre, Trinity College Dublin (TCD), Dublin, Ireland; (22) Irish Heart Foundation, Dublin, Ireland; (23) Wellcome-HRB Clinical Research Facility, St James's Hospital, Dublin, Ireland; (24) School of Medicine, Trinity College Dublin, Ireland

Abstract Background and aims International guidelines support discussion at a Neurovascular Multidisciplinary Meeting (NVMDM) to reach evidence-based decisions regarding revascularisation and/or optimal medical treatment of patients with atherosclerotic carotid artery stenosis. Data are limited on the impact the COVID-19 pandemic on performance metrics of a NVMDM. Methods This prospective audit/quality improvement project compared proportions of extracranial carotid stenosis patients in whom ‘consensus management decisions’ were reached at weekly Regional NVMDM during the ‘COVID-19’ main-pandemic (March 2020-September 2022) vs. ‘pre-COVID’ (September 2017-Febuary 2020) and ‘post-COVID’ (October 2022–February 2025) periods. We analysed adherence to NVMDM decisions in asymptomatic carotid stenosis [ACS], symptomatic carotid stenosis [SCS] and ‘indeterminate symptomatic status stenosis [ISS]’ patients, including intervals between symptom onset to NVMDM discussion +/- intervention, and post-NVMDM outcomes. Results Consensus decisions regarding management were reached in 97.9% (93/95) of COVID vs. 96.3% (104/108) of pre-COVID, and 100% (64/64) of post-COVID patients (P≥0.69). Adherence to NVMDM recommendations remained high during COVID (90.4%), pre-COVID (96.2%) and post-COVID (93.2%) periods, respectively (P≥0.10). Median intervals from index symptoms to revascularisation in 50-99% SCS patients were similar between the COVID (10.5d), pre-COVID (12.5d) and post-COVID (12.5d) periods (P≥0.24). Median intervals from NVMDM discussion to revascularisation were 3.5d (IQR: 1-7d) during the COVID period vs. 5.5d (IQR: 1-7d) during the pre-COVID period (P=0.58); vs. 3.5d (IQR: 1-7) during the post-COVID period (P=0.19). Conclusions One can maintain a high frequency of inter-speciality consensus re evidence-based management, adherence to treatment advice and guidelines regarding time-to-revascularisation of carotid stenosis patients throughout/after a pandemic. Conflict of interest No conflict of interest. Prof. McCabe's research work is supported by grant funding from several charities and organisations, including the Meath Foundation, Ireland; The Adelaide Health Foundation, Ireland; an Enterprise Ireland Innovation Partnership Programme grant with Acquis BI Technology, Ltd.; the VNRF, Ireland; and in-kind contributions from Werfen, Spain; Sysmex Ireland-UK; Sinnowa, China; Genomadix Inc., Canada and Acquis BI Technology Ltd. Note: The late Prof. Sean Tierney was instrumental to the successful conduct of our Neurovascular Multidisciplinary Meeting, and in collection and interpretation of data. The remaining members of the TUH/AMNCH Neurovascular Multidisciplinary Team who also qualify for authorship are: McCarthy AJ (1, 2, 3), Hayden D (2, 5), Coveney S (2, 5), Murphy SM (1, 3), O’Connell K (1, 2, 3), Bogdanova-Mihaylova P (1, 2, 3), Healy DA (4), Noor A (4), Walsh J (7), Ward P (7), McGrath R (7), Martin M (8), O Driscoll A (8), Smith DR (1, 3, 6), Naydonova I (1, 2, 3) and Mavridis T (1, 2): (7) Department of Radiology, Tallaght University Hospital (TUH) / The Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH) / Dublin, Ireland; (8) Naas General Hospital, Co. Kildare, Ireland

BACKGROUND:Cognitive dysfunction may be a sequelae of N-Methyl-D-Aspartate receptor encephalitis (NMDAR encephalitis) with working memory commonly affected. This study examined cognitive outcomes in patients treated for NMDAR encephalitis using a neurocognitive test battery and a working memory paradigm, compared with healthy controls & patients with schizophrenia. METHODS:Adult patients previously treated for NMDAR encephalitis were assessed using the Cambridge Automated Neuropsychological Test Battery (CANTAB) for working memory & episodic memory. Patients completed the N-back task during functional MRI (fMRI) scanning. Results were compared to patients with schizophrenia and healthy controls from a prior study. RESULTS:Twelve patients were recruited [11 women; mean (SD) age 37(12) years; Mean (SD) duration until immunotherapy treatment 7.09 (2.43) weeks]. Data were compared to 14 patients with schizophrenia [10 women; mean (SD) age 39 (12) years] and 14 healthy controls [7 women; mean (SD) age 30 (6) years]. Significant differences in letter number sequencing, spatial working memory, logical memory I, 1-back, and 2-back performance were observed (Cohen's d = 0.766 to 1.254, p< 0.05), driven by poorer performance by patients with schizophrenia. While patients with NMDAR encephalitis exhibited slightly lower performance compared with healthy controls, none of these differences were statistically significant. No significant differences in neural activation during 1-back or 2-back performance were observed. CONCLUSIONS:Study findings suggest cognitive performance in patients treated for NMDAR encephalitis approaches normal over time. Prompt treatment with immunotherapy is associated with improved cognitive outcomes. Psychiatric services should be aware of the clinical features of autoimmune encephalitis.

BACKGROUND:Simultaneously-collected data regarding platelet reactivity and activation in ischaemic cerebrovascular disease (CVD) patients starting antiplatelet agents are limited. METHODS:This prospective observational pilot study assessed platelet reactivity and activation in TIA/ischaemic stroke patients before (baseline; N = 73), 14 ± 7 days (14d; N = 59) and ≥ 90 days (90d; N = 38) after commencing aspirin or clopidogrel monotherapy. Platelet reactivity at low shear-stress (Multiplate® Aspirin/ADP assays) and platelet activation status (% expression of CD62P, CD63, and leucocyte-platelet complexes by flow cytometry) were quantified in whole blood. Prevalence of high on-treatment platelet reactivity (HTPR) was determined on Multiplate with 'case-control definitions' (Aspirin-HTPR:>40 U; Clopidogrel-HTPR:>46 U), and innovative 'longitudinal-HTPR definitions' (failure to reduce aggregation compared with the patient's baseline by more than twice the co-efficient of variation of the relevant assay). RESULTS:Prevalence of case-control aspirin-HTPR was 23.8 % at 14d and 30.8 % at 90d, and of longitudinal aspirin-HTPR was 4.8 % at 14d and 0 % at 90d. Prevalence of clopidogrel-HTPR was significantly higher with case-control than longitudinal definitions at 14d (60.5 % vs. 21 %) and 90d (52 % vs. 24 %) (P ≤ 0.03). % Neutrophil-platelet complexes (P = 0.04) and lymphocyte-platelet complexes (P = 0.002) were higher in patients with vs. without case-control clopidogrel-HTPR at 14d. Median % lymphocyte-platelet complexes significantly decreased between baseline and 14d (P = 0.019), and monocyte-platelet complexes decreased between baseline and 90d (P = 0.017) only in the clopidogrel-patient subgroup whose platelets were adequately inhibited by clopidogrel. CONCLUSIONS:Antiplatelet-HTPR prevalence is higher in CVD patients with case-control than longitudinal definitions on the Multiplate analyser. Quantifying leucocyte-platelet complexes improves our understanding of cellular mechanisms contributing to case-control clopidogrel-HTPR.

BACKGROUND:Despite international recognition of stroke as a significant health priority, discrepancies persist between the target values for stroke quality measures and the actual values that are achieved in clinical practice, referred to as gaps. This study aimed to reach consensus among international experts on prioritizing gaps in stroke care. METHODS:A two-round Delphi process was conducted, surveying an international expert panel in the field of stroke care and cerebrovascular medicine, including patient representatives, healthcare professionals, researchers, policymakers, and medical directors. Experts scored the importance and required effort to close 13 gaps throughout the stroke care continuum and proposed potential solutions. Data were analyzed using descriptive statistics and qualitative analysis methods. RESULTS:In the first and second Delphi rounds, 35 and 30 experts participated, respectively. Expert consensus was reached on the high importance of closing 11 out of 13 gaps. Two out of 13 gaps were considered moderately important to close, with expert consensus for one of these two gaps. Expert consensus indicated that only one gap, related to the prevention of complications after stroke, requires moderate effort to close, whereas the others were considered to require high effort to close. Key focus areas for potential solutions included: "Care infrastructure," "Geographic disparities," "Interdisciplinary collaboration," and "Advocacy and funding." CONCLUSIONS:While closing gaps in stroke care primarily requires high effort and substantial resources, targeted interventions in the identified key focus areas may provide feasible and clinically meaningful improvements.

In patients with atherosclerosis of the internal carotid artery (ICA), stenosis grading is commonly performed using the NASCET (North American Symptomatic Carotid Endarterectomy Trial) method. Semi-automated software techniques for computed tomography angiography (CTA) offer alternative methods. We compared the NASCET method (based on the absolute minimal diameter) with three different stenosis measurements. We analysed 519 baseline CTA scans from patients in the CONVINCE (Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke) trial. For each ICA, we calculated stenosis with semi-automated imaging software using four methods: absolute minimal diameter (NASCET method, dia[min]), area, effective diameter from area (dia[area]), and effective diameter from perimeter (dia[perim]). We assessed agreement using a weighted kappa statistic (κ), intraclass correlation coefficient (ICC) and Bland–Altman analysis. We identified 579 atherosclerotic arteries in 360 patients. Within the clinically relevant 30-99

Background Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. Methods We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (05 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. Findings 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (98%) of 1569 patients allocated to colchicine and usual care and 185 (117%) of 1575 patients allocated to usual care alone (incidence rates 332 vs 392 per 100 person-years, hazard ratio 084; 95% CI 068-105, p=012). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<005 for all timepoints). The rates of serious adverse events were similar in both groups. Interpretation Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

We describe the case of a male heavy machinery operator who presented from work with a rapidly evolving spinal cord syndrome. Spinal MRI revealed thoracic vertebral body and cord infarction and evolving mild disc prolapse attributed to fibrocartilaginous disc embolism (FCDE). FCDE should be considered as one of the aetiological mechanisms of acute spinal cord infarction in pile-driver/heavy machinery operators, especially in association with adjacent vertebral body infarction and intervertebral disc prolapse. Magnetic resonance imaging (MRI) changes may evolve, warranting early follow-up MRI in appropriate cases.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke.In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays).VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04).Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

Background/aims Data are limited on the frequency of ‘consensus decisions’ between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM ‘adherence’ to such advice. Methods This prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom ‘consensus management decisions’ were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), ‘indeterminate symptomatic status stenosis’ (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / − intervention. Results One hundred fifteen patients were discussed: 108 with carotid stenosis and 7 with VAS. Consensus regarding management was noted in 96.5% (111/115): 100% with ACS and VAS, 96.2% with SCS and 92.9% with ISS. Adherence to MDM management advice was 96.4% (107/111): 100% in ACS, ISS and VAS patients; 92% (46/50) in SCS patients. The median interval from index symptoms to revascularisation in 50–99% SCS patients was 12.5 days (IQR: 9–18.3 days; N = 26), with a median interval from MDM to revascularisation of 5.5 days (IQR: 1–7 days). Thirty patients underwent revascularisation. Two out of twenty-nine patients (6.9%) with either SCS or ISS had a peri-procedural ipsilateral ischaemic stroke, with no further strokes/deaths during 3-months follow-up. Conclusions The high frequency of inter-specialty consensus regarding management and adherence to proposed treatment supports a collaborative/multidisciplinary model of care in patients with extracranial arterial stenoses. Service development should aim to shorten times between MDM discussion-intervention and optimise prevention of stroke/death.

therapy ARR Absolute risk reduction ARWMC Age related white matter change AF Atrial fibrillation BA Basilar artery BES Balloon expandable stent BMS Bare metal stent

BackgroundRecently-released ‘Reticulated Platelets (RP)’ may contribute to High on-Treatment Platelet Reactivity (HTPR). Data in TIA/ischaemic stroke are limited.AimsAssess relationship between%RP fraction (%RPF) and ex-vivo Aspirin-HTPR status under high and low shear stress conditions after TIA/ischaemic stroke.MethodologyData from two prospective observational studies were collated on%RPF in TIA/ischaemic stroke patients at 14days (N=141) and ≥90days (N=68) on Aspirin alone/in combination with Dipyridamole or Clopidogrel using an ‘automated assay’ (Sysmex XE-2100TM/XN-9100TM). Aspirin-HTPR was defined at moderately-high shear stress as ‘closure times’ ≥176s on PFA-100® Collagen-Epinephrine assays, and at low shear stress as ‘Aspirin Reaction Units (ARU)’ ≥550 on VerifyNow® Aspirin assays. We compared ‘unad- justed%RPF’ between patients with vs. without HTPR; Spearman rank correlation assessed relationships between%RPF and platelet reactivity.ResultsAspirin-HTPR prevalence at 14d-≥90d, respectively, was 45.1%-33.8% on PFA-100, and 4.4%-12.3% on VerifyNow. In patients with vs. without HTPR on PFA-100,%RPF was not statistically-significantly higher at 14d (3.15 vs. 2.8%, P=0.2), but was higher at ≥90d (3.6 vs. 2.1%, P=0.002). There was a negative correlation between%RPF and PFA-100 closure times at ≥90d (Spearman-ρ=-0.267; P=0.036).DiscussionReticulated platelets contribute to Aspirin-HTPR under high shear stress conditions in the late phase after TIA/ischaemic stroke.

Background/AimsData are limited on the influence of the COVID-19 pandemic on consensus deci- sion-making at a neurovascular multidisciplinary meeting (MDM) in patients with extracranial carotid/vertebral stenoses.MethodsThis prospective audit/quality-improvement project compared proportions of extracranial carotid stenosis patients in whom ‘consensus management decisions’ were reached at a weekly Neuro- vascular/Stroke Centre MDM in the COVID-19 ‘pandemic’ (March/2020-September/2022) vs. ‘pre-pan- demic’ period (September/2017-Febuary/2020). Adherence to MDM decisions was analysed in asymp- tomatic carotid stenosis [ACS], symptomatic carotid stenosis [SCS] and ‘indeterminate symptomatic status stenosis [ISS]’ patients.ResultsConsensus regarding management was 98% (97/99) in pandemic vs. 96.5% (111/115) in pre-pan- demic patients overall (P=0.59); i.e. 98% (51/52) with SCS, 100% (23/23) with ACS, and 98% (23/24) with ISS during the pandemic. Adherence-to-advice was 91% (90/99) in pandemic vs. 96.4% (107/111) in pre-pandemic patients (P=0.10); i.e. 88% (46/52) with SCS, 96% (22/23) with ACS, and 92% (22/24) with ISS during the pandemic. Comparing pandemic vs. pre-pandemic periods, median interval from index TIA/stroke-to-revascularisation for 50-99% SCS was 11 days (IQR:8.8-15.8d) vs. 12.5days (IQR:9-18d; P=0.30), and from MDM-to-revascularisation was 3d (IQR:1-7d) vs. 5.5d (IQR:1-7d; P=0.58).ConclusionsThe COVID-19 pandemic did not adversely influence frequency of consensus regarding management, adherence to MDM advice, or intervals-to-revascularisation in carotid stenosis patients.

Abstract Background An estimated 64,000 people currently live with dementia in Ireland, with this number expected to rise to 150,000 by 2045. For every one person with dementia, there are approximately three others providing support and care. Caregivers can often undergo a decline in physical and mental health and experience feelings of isolation and loneliness. Caregiver education and support can help to mitigate these challenges. Lecture based programmes on their own have a limited effect on understanding the lived experience of the person with dementia, whereas including simulation based empathy building elements can lead to better quality outcomes for caregivers and the person with dementia. A multi-component education programme for family caregivers incorporating dementia simulation, was devised and implemented over 7 weeks. Topics included dementia awareness, delirium, communication, non-cognitive symptoms, self-care, and accessing practical community supports. Methods A survey measuring Person-reported outcomes (PROMS) and Person-reported experience (PREMS) was conducted with 14 caregivers attending two pilot groups. Results 100% of participants felt that the group enhanced their knowledge of dementia and increased their confidence in supporting their loved one as dementia progresses and in relation to non- cognitive symptoms. 100% of the participants found that peer support was extremely beneficial. They also felt that the group was welcoming and felt comfortable sharing in the group. All participants indicated that dementia simulation helped increase understanding of what it is like to have dementia, often reframing their relationship with their loved one. Conclusion The benefits of peer supports and dementia awareness education for caregivers are well documented and this survey supports these assumptions. However, for caregivers the addition of dementia simulation scenarios and role play enhanced their understanding of the lived experience of people with dementia, building empathy and confidence in their role, decreasing stress and leading to changes in caregiving approach.

BackgroundData are limited on thrombin generation biomarker profiles in carotid stenosis patients with or without cerebral micro-embolic signals (MES).Aims andMethodsIn this prospective, multi-centre, observational study, plasma thrombin generation parameters were compared in patients with ≥50-99% asymptomatic(N=34) vs. symptomatic carotid stenosis in the early (≤4 weeks; N=39) and late phases (≥3 months; N=31) after TIA/ischaemic stroke. Nested longitudinal follow-up was performed in symptomatic patients. Transcranial Doppler ultrasound classified patients as MES+ve or MES-ve.ResultsThere were no significant differences in thrombin generation parameters between early or late symptomatic vs. asymptomatic patients (P≥0.17). In symptomatic patients with matched data at each timepoint, peak thrombin production (365.1 vs. 327.2nM; P=0.003) and endogenous thrombin potential (2242.6 vs. 2078.4 nM*min; P=0.048) decreased between the early and late phases overall. The fall in peak thrombin during follow-up was significant in symptomatic subgroups who underwent revascularisation (N=26; P=0.007) and who were MES-ve (N=14; P=0.029), but not in those on optimal medical therapy alone (N=5; P=0.19).DiscussionThrombin generation decreases over time and following revascularisation in TIA/stroke patients with moderate-severe symptomatic carotid stenosis, including those who are MES-ve. These data improve our understanding of haemostatic/thrombotic biomarker profiles in patients with carotid stenosis.

Objective: The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or symptomatic atherosclerotic carotid stenosis. Data Sources: Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Review Methods: A systematic review collated data from 1975 to 2020 on ex vivo platelet activation and platelet function/reactivity in patients with atherosclerotic carotid stenosis. Results: Forty-three studies met the inclusion criteria; the majority included patients on antiplatelet therapy. Five studies showed increased platelet biomarkers in patients with >= 30% asymptomatic carotid stenosis (ACS) vs. controls, with one neutral study. Preliminary data from one study suggested that quantification of "coated platelets" in combination with stenosis severity may aid risk stratification in patients with >= 50% - 99% ACS. Platelets were excessively activated in patients with >= 30% symptomatic carotid stenosis (SCS) vs. controls (>= 11 positive studies and one neutral study). Antiplatelet-High on Treatment Platelet Reactivity (HTPR), previously called "antiplatelet resistance", was observed in 23% - 57% of patients on aspirin, with clopidogrel-HTPR in 25% - 100% of patients with >= 50% - 99% ACS. Aspirin-HTPR was noted in 9.5% - 64% and clopidogrel-HTPR in 0 - 83% of patients with >= 50% SCS. However, the data do not currently support the use of ex vivo platelet function/reactivity testing to tailor antiplatelet therapy outside of a research setting. Platelets are excessively activated (n = 5), with increased platelet counts (n = 3) in recently symptomatic vs. asymptomatic patients, including those without micro-emboli on transcranial Doppler (TCD) monitoring (n = 2). Most available studies (n = 7) showed that platelets become more reactive or activated following carotid endarterectomy or stenting, either as an acute phase response to intervention or pen-procedural treatment. Conclusion: Platelets are excessively activated in patients with carotid stenosis vs. controls, in recently symptomatic vs. asymptomatic patients, and may become activated/hyper-reactive following carotid interventions despite commonly prescribed antiplatelet regimens. Further prospective multicentre studies are required to determine whether models combining clinical, neurovascular imaging, and platelet biomarker data can facilitate optimised antiplatelet therapy in individual patients with carotid stenosis.