Imelda Noone

Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence.

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.

Plaque Inflammation and Unstable Morphology Are Associated With Early Stroke Recurrence in Symptomatic Carotid Stenosis

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 <2; 50% versus 6.3%; 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 <3 (log-rank P=0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or <3), age, and severity of stenosis (50%–69% or ≥70%), plaque inflammation was the only variable independently predicting stroke recurrence (adjusted hazard ratio, 9; confidence interval, 1.1–70.6; 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.

Assessment and management of transient ischaemic attack--the role of the TIA clinic.

BackgroundAs the risk of early stroke following transient ischaemic attack (TIA) is increasingly recognised, the management of patients presenting with symptoms suggestive of TIA presents a clinical challenge.MethodsAnalysis of prospectively collected data on patients referred to a TIA clinic in St. Vincent’s University Hospital, between January 2003 and July 2004.ResultsOne-hundred- and -seventeen (117) patients (mean age 75.5 years) were assessed. The majority (79%) were referred from Accident and Emergency and 61% were seen within one week of referral. Seventy-two patients (62%) had a final diagnosis of cerebrovascular disease (56 TIA, 16 completed strokes), of whom five (7%) and four (5.5%) had severe (> 70%) and moderate (> 50%) symptomatic carotid artery stenosis, respectively, whilst seven patients (10%) had newly diagnosed atrial fibrillation, five of whom were anticoagulated. Non-cerebrovascular diagnoses were made in twenty-seven patients (24%).ConclusionA TIA clinic, in co-ordination with Accident & Emergency Services, provides a safe and efficient alternative to hospital admission for patients with TIA symptoms and a low early stroke risk.

Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic carotid plaque

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 18fluorodeoxyglucose (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 (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Results: Sixty-one patients were included. Plaque inflammatory FDG SUVmax 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 SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho −0.37, p = 0.004) and SUVROImax (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 SUVmax. 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.

Antithrombotic treatment at onset of stroke with atrial fibrillation, functional outcome, and fatality: a systematic review and meta-analysis

Background In atrial fibrillation–associated stroke, conflicting data exist regarding association between therapeutic vitamin K-antagonist anticoagulation (International Normalized Ratio 2–3) and early death and functional outcome, and few data exist relating to late outcome in ischemic and haemorrhagic atrial fibrillation–stroke. Aim We performed a systematic review and meta-analysis of oral anticoagulation at stroke onset, death and functional outcome. Methods We performed a systematic review, searching multiple sources. Studies were included if outcomes in atrial fibrillation–associated stroke were reported stratified by pre-stroke antithrombotic status, with documented International Normalized Ratio at onset. Outcomes were survival and good functional outcome (modified Rankin score 0–2) at discharge/30 days, and at one-year. Results Of eight studies (3552 patients) in ischemic stroke, International Normalized Ratio ≥ 2 compared with other treatments (International Normalized Ratio < 2, antiplatelet, or no anti-thrombotic) was associated with good outcome [pooled odds ratio 1·9 (95% confidence interval) 1·5–2·5, P < 0·001] and improved survival at 30 days discharge (pooled odds ratio for death 0·4, confidence interval 0·2–0·5, P < 0·001). The net benefit remained after inclusion of haemorrhagic stroke (odds ratio for good outcome 1·89, confidence interval 1·45–2·46, P < 0·001). At one-year, improved functional outcome for International Normalized Ratio ≥ 2 (pooled odds ratio 1·7, confidence interval 1·0–2·7, P = 0·04) and survival (odds ratio for death 0·5, confidence interval 0·4–0·8, P = 0·001) were also observed. Conclusions Therapeutic International Normalized Ratio at stroke onset was associated with early and late improved survival and functional recovery suggesting sustained benefit for warfarin anticoagulation for stroke outcome in atrial fibrillation patients. Long-term outcome data following stroke in patients taking new oral anticoagulants is required.

A comparison of service organisation and guideline compliance between two adjacent European health services

Introduction Outcomes in stroke patients are improved by a co-ordinated organisation of stroke services and provision of evidence-based care. We studied the organisation of care and application of guidelines in two neighbouring health care systems with similar characteristics. Methods Organisational elements of the 2015 National Stroke Audit (NSA) from the Republic of Ireland (ROI) were compared with the Sentinel Stroke National Audit Programme (SSNAP) in Northern Ireland (NI) and the United Kingdom (UK). Compliance was compared with UK and European guidelines. Results Twenty-one of 28 ROI hospitals (78%) reported having a stroke unit (SU) compared with all 10 in NI. Average SU size was smaller in ROI (6 beds vs. 15 beds) and bed availability per head of population was lower (1:30,633 vs. 1:12,037 p < 0.0001 Chi Sq). Fifty-four percent of ROI patients were admitted to SU care compared with 96% of UK patients (p < 0.0001). Twenty-four–hour physiological monitoring was available in 54% of ROI SUs compared to 91% of UK units (p < 0.0001). There was no significant difference between ROI and NI in access to senior specialist physicians or nurses or in SU nurse staffing (3.9/10 beds weekday mornings) but there was a higher proportion of trained nurses in ROI units (2.9/10 beds vs. 2.3/10 beds (p = 0.02 Chi Sq). Conclusion Whilst the majority of hospitals in both jurisdictions met key criteria for organised stroke care the small size and underdevelopment of the ROI units meant a substantial proportion of patients were unable to access this specialised care.

047The Effectiveness of Stroke Rehabilitation in Older Old Patients Compared to a Group of Younger Stroke Patients

Background: The benefits of rehabilitation post stroke are widely accepted. However, the older old (patients over 80) are underrepresented in previous studies. We aimed to examine whether the benefits differ based on age. Method: All patients admitted to a specialist inpatient rehabilitation hospital post stroke between 2010–2016 were included. Patients were assessed for rehabilitation potential prior to transfer and received an individualised interdisciplinary rehabilitation programme. Admission and discharge Barthel scores were recorded. We analysed the change in Barthel index (BI) and length of stay (LOS) by age group. Results: 185 patients were included, 10 of these were excluded due to death, becoming unwell and self-discharge. Patients (47% men, mean age 77.8, 83% ischaemic strokes) were generally previously independent (81% modified Rankin 0–1). 32.6% of patients admitted for rehabilitation showed no evidence of cognitive impairment, 29.1% had mild cognitive impairment, 22.9% moderate cognitive impairment and 11.4% severe cognitive impairment. Mean increase in Barthel did not differ across the age groups and there was no significant difference in LOS. For all age groups, the mean BI on admission was 13 (4.7 SD), 15.6 on discharge (4.34 SD) with a mean LOS of 82 days. In the under 65’s (n = 13), the mean BI on admission was 13.8 (6.1 SD), 16.1 (4.9 SD) on discharge with a mean LOS of 78 days (70 SD). Over 85 s (n = 35), mean BI on admission 11(4.2 SD), 13.3 (4.8 SD) on discharge, LOS 89 days (67 SD).The mean change in BI was 2.9 for the 76–85 group and 2.3 for other age groups. p values for BI change and LOS trends across age groups were non-significant. 81% of patients were discharged home. Conclusion: Stroke rehabilitation can be as effective in older old people as in younger people. Age should not be a barrier to access rehabilitation and selection criteria should be the same as their younger counterparts.

135The First 6 Hours in a Stroke Patient’s Journey

Background: Hyperacute treatments using acute reperfusion therapy (ART) are now standard practice in stroke. The benefits of these treatments are time dependent, hence the primary focus of management is the rapid diagnosis and delivery of a reperfusion therapy to an appropriate patient. Our audit aimed to examine the standard of care received by patients who present with neurological symptoms within 6 hours of onset, using the RCP London 2016 guidelines. Methods: Retrospective analysis of stroke patients presenting within 6 hours of stroke symptoms. The clinical assessment and radiological imaging were reviewed and the clinical decision making for or not for ART was examined. Results: 97 new stroke patients were admitted during a 5-month period (March–July 2016). Average age was 79 years with equal male: female ratio. 47.4% (n = 46) presented within 6 hours of symptoms onset. Of these,15 (32.6%) received ART in forms of intravenous thrombolysis (n = 8) or thrombectomy (n = 4). 3 patients had both treatment. Our thrombolysis rate was 11%. Median time from symptoms onset to emergency department (ED) triage was 105 mins (30–280 mins) and median time from triage to CT brain was 40 mins (10–950 mins). Our average door to needle time was 66.5 mins (20–127 mins). Those who received ART, were younger (mean age 77 years vs 79.6 years), more independent (80% with pre-stroke mRS 0–1 vs 48.4%), and presented earlier to ED (median time from symptoms onset to ED triage 90 mins vs 127 mins). 31 patients received no ART. Most common reasons for not offering treatment include: minor stroke (22%), intracranial haemorrhage (16%), and rapid resolution of symptoms (9%). 35% had no clear documentation of contraindications to treatment. Conclusion: Our thrombolysis rate of 11% is in line with national average. There is good compliance with guidelines in brain imaging, appropriate candidate selection and prompt delivery of treatment. However, documentation of clinical decisions in those who received no ART remains poor.

220New and Old Atrial Fibrillation in Stroke Patients. Two Different Tales

Background: Atrial fibrillation (AF) is a known risk factor for stroke disease and anticoagulation has a relative risk reduction of 60 – 70% for the prevention of stroke. Not all patients with known AF receive anticoagulation. In addition, 20% of stroke patients with AF have strokes unrelated to their AF. Methodology: In 2016, 383 patients were admitted to our hospital with a confirmed stroke. We compared data on patients who were admitted with confirmed (known) AF and those who were newly identified as AF. Results: A total of 101 (26%) patients had AF. 67 (66.3%) patients had known AF. Comparing the known and new AF, there was no difference in age or sex distribution. 39 (58%) of the known AF were on an oral anticoagulant (OAC); 18 (46.2%) of these patients were on warfarin with a mean INR on admission of 1.95. 21 (54%) were on a direct oral anticoagulant (DOAC). 15 (22%) of the known AF presented with an intra-cerebral haemorrhage (ICH) compared with 2 (5.8%) in the new AF population. 10 (66.7%) of the ICHs in the known AF cohort were on a DOAC compared with 3 (20%) on warfarin. Comparing outcomes, 40-patients (59.7%) had a good outcome (discharge home) in the known AF group compared to 21 (61.7%) in the new AF. 27 (40.3%) had a bad outcome (discharge to nursing home/death)in the known AF group compared to 13 (38.2%) in the new AF. This shows no significant difference overall, however, there was a higher rate of mortality in the known-17 (25.4%) compared to the new AF-2 (5.9%) (p.0001). Conclusion: A significant number of stroke patients have AF on admission and a third are new cases. For those patients with known AF, a significant number are still not anticoagulated in the community. A higher number of ICHs were seen in the known AF group and more commonly in those on a DOAC. The known AF group is at a higher risk of a bad outcome post stroke.