Intravenous Thrombolysis with Tenecteplase for the Treatment of Acute Ischemic Stroke.

OBJECTIVE: Intravenous thrombolysis (IVT) with tenecteplase has been associated with better clinical outcomes in acute ischemic stroke (AIS) patients with confirmed large vessel occlusions compared to IVT with alteplase. However, the utility of tenecteplase for the treatment of all AIS patients eligible for IVT has not been established. METHODS: We compared the safety and efficacy of tenecteplase versus alteplase in AIS patients by analyzing propensity score matched data from 20 centers participating in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients receiving IVT with tenecteplase were matched with up to 3 patients receiving alteplase from the same center. The primary outcome of interest was the distribution of 3-month functional outcomes. Secondary outcomes included the rates of patients with symptomatic intracranial hemorrhage (SICH) in the first 24 hours, excellent (modified Rankin Scale [mRS] score = 0-1) or good (mRS score = 0-2) functional outcome, and all-cause mortality at 3 months. RESULTS: A total of 331 tenecteplase-treated AIS patients were matched to 797 patients treated with alteplase (median age = 70 years, 43.9% women, median National Institutes of Health Stroke Scale score = 11, interquartile range = 6-17). Patients treated with tenecteplase had better 3-month functional outcomes (common odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.18-2.00) with higher odds of good functional outcome (OR = 2.00, 95% CI = 1.45-2.77) and a lower likelihood of all-cause mortality (OR = 0.43, 95% CI = 0.27-0.67) at 3 months, compared to alteplase-treated patients. No difference was found in the likelihood of the 3-month excellent functional outcomes (OR = 1.31, 95% CI = 0.96-1.78) and 24-hour SICH (1.0% vs 1.3%, OR = 0.72, 95% CI = 0.20-2.64). INTERPRETATION: IVT with tenecteplase was associated with better 3-month clinical outcomes compared to IVT with alteplase in AIS patients, with no increased risk of symptomatic intracranial bleeding. ANN NEUROL 2022;92:349-357.

Screening for silent aspiration in hyperacute stroke: A feasibility study of clinical swallowing examination and cough reflex testing.

BACKGROUND: Silent aspiration (SA) is common post-stroke and associated with increased risk of pneumonia, length of stay and healthcare costs. Clinical swallow examinations (CSEs) are unreliable measures of SA. There is no consensus on the clinical components that best detect SA. Cough reflex testing (CRT) is an alternative/adjunct whose SA detection accuracy also lacks consensus. AIMS: To investigate the feasibility of CSE versus CRT against gold standard flexible endoscopic evaluation of swallowing (FEES) for SA identification and to estimate its prevalence in a hyperacute stroke setting. METHODS & PROCEDURES: A single-arm preliminary, prospective, feasibility study of patients less than 72 h post-stroke, over a 31-day period on a hyperacute stroke unit: the Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. Ethical approval for the study was obtained. The study tested the feasibility and acceptability of introducing CRT and developing a standardized CSE. Consent/assent was obtained for all participants. Patients unfit for study were excluded. OUTCOMES & RESULTS: A total of 62% of patients less than 72 h post-stroke (n = 61) were eligible. A total of 75% of those approached (n = 30) consented. A total of 23 patients completed all tests. The principal barrier was anxiety regarding FEES. Mean test time for CRT = 6 min; CSE = 8 min; FEES = 17 min. Patients rated CRT and FEES on average as moderately uncomfortable. A total of 30% (n = 7) of participants who received FEES presented with SA. CONCLUSIONS & IMPLICATIONS: CRT, CSE and FEES are feasible in 58% of hyperacute stroke patients in this setting. FEES anxiety is the main recruitment barrier and is not always well tolerated. Results support further work to establish optimum methods and differential sensitivity/specificity of CRT and CSE in hyperacute stroke for SA identification. WHAT THIS PAPER ADDS: What is already known on this subject SA significantly increases the risk of pneumonia in the early days post-stroke. CSEs are unreliable for identification of SA risk in this population. CRT is gaining popularity as a potential tool to identify stroke patients at risk of SA, though there are questions regarding the efficacy of the clinical protocol currently being used in the UK. What this study adds to existing knowledge This study demonstrates that it is practical and feasible to carry out a larger scale study in this setting to compare CSE and CRT including a consideration of an approach combining both methods for clinical identification of SA versus FEES. Preliminary findings suggest that CSE may have higher levels of sensitivity than CRT for SA identification. What are the potential or actual clinical implications of this work? The results of this study suggest that further work is needed to establish the optimum methods and differential sensitivity/specificity of clinical tools for SA detection in hyperacute stroke.

The Effect of the 2019 Novel Coronavirus Pandemic on Stroke and TIA Patient Admissions: Perspectives and Risk Factors.

BACKGROUND: The 2019 novel coronavirus pandemic has generated concern from stroke specialist centres across the globe. Reductions in stroke admissions have been reported, despite many expecting an increase due to the pro-thrombotic nature of 2019 novel coronavirus. AIMS: To assess the impact of the pandemic and subsequent lockdown on stroke admissions and transient ischaemic attack referrals at the Royal Victoria Infirmary, Newcastle-Upon-Tyne, and additionally on patient behaviours affecting modifiable risk factors or perspectives related to accessing healthcare. METHODS: A single-centre retrospective data analysis was carried out on a "lockdown" cohort of suspected stroke patients admitted between 11 March to 26 May 2020 and a "pre-lockdown" cohort admitted in 2019. Differences in weekly admissions, weekly referrals, onset-to-presentation time and weekly thrombolysis cases were examined. Further analysis interrogated these cohorts separated by Bamford classification and stroke mimics (such as seizure/hemiplegic migraine/functional neurology). A binary-format questionnaire was separately administered to admitted patients from 15 April to 5 June 2020. RESULTS: Significant reductions in weekly posterior circulation infarct (-43%, p = 0.017) and stroke-mimic (-47%, p < 0.001) admissions and weekly referrals diagnosed as non-transient ischaemic attack (-55%, p = 0.002) were observed in the lockdown cohort, with no differences in onset-to-presentation time. Over 25% of questionnaire respondents reported less physical activity, increased isolation and delaying their presentation due to the pandemic. CONCLUSIONS: This study provides evidence of reduced stroke-mimic and posterior circulation infarct admissions. Questionnaire findings suggest that patients need to be informed to ensure they appropriately seek medical advice. Significant communication at the stroke-primary care interface is needed to support referral pathways and management of modifiable risk factors.

Bolus-Infusion Delays of Alteplase during Thrombolysis in Acute Ischaemic Stroke and Functional Outcome at 3 Months.

Background. The efficacy of alteplase in acute ischaemic stroke (AIS) is highly time dependent. Hence, alteplase is administered as soon as possible with a bolus followed by an infusion. Delays between bolus and infusion may occur, but the extent of these delays and the impact on outcome are unclear. Aims. We investigated the extent of bolus-infusion delays and the relationship between delays and stroke outcome. Method. We reviewed medical records of 276 patients who received alteplase for AIS at our centre between April, 2008, and June, 2013. Complete demographic and clinical data including 3-month modified Rankin Score (mRS) from 229 patients were analysed comparing delays of 0-8 and >8 minutes. Results. Overall mean (SD) bolus-infusion delay was 9 (7) minutes. Baseline characteristics were similar apart from more severe strokes in delays >8 minutes. Three-month outcomes were not significantly different although delays >8 minutes had lower functional independence rate (mRS 0-1: 23.1% versus 28.1%; adjusted OR 1.2 (95% CI 0.6 to 2.4, P = 0.68)) and higher mortality rate (18% versus 11%, OR 1.0, 95% CI 0.6 to 1.7, P = 0.95). Conclusions. In this single centre series, bolus-infusion delays of alteplase in AIS were common and no effect of bolus-infusion delays on independence and mortality was found.

The SOAR (Stroke subtype, Oxford Community Stroke Project classification, Age, prestroke modified Rankin) score strongly predicts early outcomes in acute stroke.

BACKGROUND: Previous prognostic scoring systems in predicting stroke mortality are complex, require multiple measures that vary with time and failed to produce a simple scoring system. AIMS/HYPOTHESIS: The study aims to derive and internally validate a stroke prognostic scoring system to predict early mortality and hospital length of stay. METHODS: Data from a U.K. multicenter stroke register were examined (1997-2010). Using a prior hypothesis based on our and others observations, we selected five patient-related factors (age, gender, stroke subtype, clinical classification, and prestroke disability) as candidate prognostic indicators. An 8-point score was derived based on multiple logistic regression model using four out of five variables. Performance of the model was assessed by plotting the estimated probability of in-hospital death against the actual probability by testing for overfitting (calibration) and area under the curve methods (discrimination). RESULTS: The total sample consisted of 12,355 acute stroke patients (ischemic stroke 91.0%). The score predicted both in-patient and seven-day mortality. The crude in-patient mortality were 1.57%, 4.02%, 10.65%, 21.41%, 46.60%, 62.72%, and 75.81% for those who scored 0, 1, 2, 3, 4, 5, and 6, respectively. The calibration of the model revealed no evidence of overfitting (estimated overfitting 0.001). The area under the curve values for both in-hospital and seven-day mortality were 0.79. The score predicted length of stay with a higher score was associated with longer median length of stay in those discharged alive and shorter median length of stay in those who died (P for both <0.001). CONCLUSIONS: A simple 8-point clinical score is highly predictive of acute stroke mortality and length of hospital stay. It could be used as prognostic tool in service planning and also to risk-stratify patients to use these outcomes as markers of stroke care quality across institutions.

Association between prestroke disability and inpatient mortality and length of acute hospital stay after acute stroke.

OBJECTIVES: To examine the prognostic value of prestroke disability in predicting inpatient mortality and length of hospital stay (LOS) independent of age, sex, and stroke type and severity. DESIGN: Retrospective analysis of prospectively collected stroke registers. SETTING: United Kingdom. PARTICIPANTS: Fourteen thousand four hundred thirty-seven individuals (52.9% female, mean age 75.4 ± 12.1) with stroke (82% ischemic) admitted to three university hospitals. MEASUREMENTS: Data were examined from three hospital registers: Aintree (2005-2010), Newcastle (2000-2005), and Norwich (1997-2010). Risk of inpatient death and prolonged hospital stay according to prestroke disability using the modified Rankin Score (mRs) were assessed using logistic regression adjusting for age, sex, and stroke subtype (ischemic vs hemorrhagic) and severity. RESULTS: Inpatient death was 20.8%. In fully adjusted models, higher prestroke mRs was associated with significantly greater risk of mortality (for mRs = 1, 2, 3, 4, and 5 vs mRs = 0: odds ratio (OR)=1.28, 95% confidence interval (CI)=1.09-1.50; OR = 1.50, 95% CI = 1.29-1.75; OR = 1.85, 95% CI = 1.60-2.13; OR = 2.56, 95% CI = 2.15-3.04; and OR = 4.48, 95% CI = 3.47-5.80, respectively). The relationship appeared to be linear, and each point increase in mRs equated to being approximately 5 years older. Although age and stroke type appear to be strong independent predictors of LOS, premorbid mRs also predicted longer LOS regardless of discharge status. The predictability of the model using these parameters was very good (receiver operating characteristic: 0.82 for death and 0.65-0.70 for LOS). CONCLUSION: Prestroke disability predicts inpatient death and LOS, independent of age, sex, and stroke type and severity. Whether this is related to mental or physical disability should be examined in future prospective studies.