Intravenous thrombolysis is the only approved systemic reperfusion treatment for patients with acute ischaemic stroke. These European Stroke Organisation (ESO) guidelines provide evidence-based ...recommendations to assist physicians in their clinical decisions with regard to intravenous thrombolysis for acute ischaemic stroke. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Expert consensus statements were provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high quality evidence to recommend intravenous thrombolysis with alteplase to improve functional outcome in patients with acute ischemic stroke within 4.5 h after symptom onset. We also found high quality evidence to recommend intravenous thrombolysis with alteplase in patients with acute ischaemic stroke on awakening from sleep, who were last seen well more than 4.5 h earlier, who have MRI DWI-FLAIR mismatch, and for whom mechanical thrombectomy is not planned. These guidelines provide further recommendations regarding patient subgroups, late time windows, imaging selection strategies, relative and absolute contraindications to alteplase, and tenecteplase. Intravenous thrombolysis remains a cornerstone of acute stroke management. Appropriate patient selection and timely treatment are crucial. Further randomized controlled clinical trials are needed to inform clinical decision-making with regard to tenecteplase and the use of intravenous thrombolysis before mechanical thrombectomy in patients with large vessel occlusion.
Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of ...recurrent stroke is unknown.
In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete.
Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 90% CI 0·79–1·24), 99 (22%) of 450 in the asundexian 20 mg group (1·15 0·93–1·43), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 0·85–1·32; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 90% CI 0·91–2·71).
In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke.
Bayer AG.
Objective
This study was undertaken to investigate the efficacy, tolerability, and outcome of different timing of anesthesia in adult patients with status epilepticus (SE).
Methods
Patients with ...anesthesia for SE from 2015 to 2021 at two Swiss academic medical centers were categorized as anesthetized as recommended third‐line treatment, earlier (as first‐ or second‐line treatment), and delayed (later as third‐line treatment). Associations between timing of anesthesia and in‐hospital outcomes were estimated by logistic regression.
Results
Of 762 patients, 246 received anesthesia; 21% were anesthetized as recommended, 55% earlier, and 24% delayed. Propofol was preferably used for earlier (86% vs. 55.5% for recommended/delayed anesthesia) and midazolam for later anesthesia (17.2% vs. 15.9% for earlier anesthesia). Earlier anesthesia was statistically significantly associated with fewer infections (17% vs. 32.7%), shorter median SE duration (.5 vs. 1.5 days), and more returns to premorbid neurologic function (52.9% vs. 35.5%). Multivariable analyses revealed decreasing odds for return to premorbid function with every additional nonanesthetic antiseizure medication given prior to anesthesia (odds ratio OR = .71, 95% confidence interval CI = .53–.94) independent of confounders. Subgroup analyses revealed decreased odds for return to premorbid function with increasing delay of anesthesia independent of the Status Epilepticus Severity Score (STESS; STESS = 1‐2: OR = .45, 95% CI = .27–.74; STESS > 2: OR = .53, 95% CI = .34–.85), especially in patients without potentially fatal etiology (OR = .5, 95% CI = .35–.73) and in patients experiencing motor symptoms (OR = .67, 95% CI = .48–.93).
Significance
In this SE cohort, anesthetics were administered as recommended third‐line therapy in only every fifth patient and earlier in every second. Increasing delay of anesthesia was associated with decreased odds for return to premorbid function, especially in patients with motor symptoms and no potentially fatal etiology.
What is a minor stroke? Fischer, Urs; Baumgartner, Adrian; Arnold, Marcel ...
Stroke (1970),
04/2010, Letnik:
41, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The term "minor stroke" is often used; however a consensus definition is lacking. We explored the relationship of 6 "minor stroke" definitions and outcome and tested their validity in subgroups of ...patients.
A total of 760 consecutive patients with acute ischemic strokes were classified according to the following definitions: A, score < or = 1 on every National Institutes of Health Stroke Scale (NIHSS) item and normal consciousness; B, lacunar-like syndrome; C, motor deficits with or without sensory deficits; D, NIHSS < or = 9 excluding those with aphasia, neglect, or decreased consciousness; E, NIHSS < or = 9; and F, NIHSS < or = 3. Short-term outcome was considered favorable when patients were discharged home, and favorable medium-term outcome was defined as a modified Rankin Scale score of < or = 2 at 3 months. The following subgroup analyses were performed by definition: sex, age, anterior versus posterior and right versus left hemispheric stroke, and early (0 to 6 hours) versus late admission (6 to 24 hours) to the hospital.
Short-term and medium-term outcomes were most favorable in patients with definition A (74% and 90%, respectively) and F (71% and 90%, respectively). Patients with definition C and anterior circulation strokes were more likely to be discharged home than patients with posterior circulation strokes (P=0.021). The medium-term outcome of older patients with definition E was less favorable compared with the outcome of younger ones (P=0.001), whereas patients with definition A, D, and F did not show different outcomes in any subgroup.
Patients fulfilling definition A and F had best short-term and medium-term outcomes. They would be best suited to the definition of "minor stroke."
There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID‐19), but little is known regarding whether they reflect structural damage to the nervous ...system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID‐19 patients, 10 critically ill non–COVID‐19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID‐19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short‐term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610–616
It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary ...prevention should be managed.
We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists VKA or direct oral anticoagulants DOAC) prior to index event (OAC
) with those without prior oral anticoagulation (OAC
). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC
) with those who continued the same anticoagulation as secondary prevention (OAC
). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
We included 5,413 patients (median age = 78 years interquartile range (IQR) = 71-84 years; 5,136 96.7% had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 IQR = 2-12). The median CHA
DS
-Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OAC
(n = 1,195) and OAC
(n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OAC
was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OAC
(n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OAC
(n = 585).
Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA
DS
-Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.
Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it ...is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk.
Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation.
Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death.
Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54.
Objective
The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral ...anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes.
Methods
This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months.
Results
Of 8,179 patients (mean SD age, 79.8 9.6 years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, interquartile range 2–11) compared with VKA (6, 2–14) and controls (7, 3–15, p < 0.001; quantile regression: β −2.1, 95% confidence interval CI −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 63%; adjusted odds ratio aOR 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 15%; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 74%). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51).
Interpretation
Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53
Objective
We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.
...Methods
We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow‐up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke AIS, intracerebral hemorrhage ICH, or mortality) using mixed‐effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).
Results
We included 4,912 patients (median age, 78 years interquartile range {IQR}, 71–84; 2,331 47.5% women; median National Institute of Health Stroke Severity Scale at onset, 5 IQR, 2–12); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2–14) for VKAs and 5 days (IQR, 2–11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow‐up of 5,970 patient‐years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67–1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24–0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70–1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68–1.03; p = 0.09).
Interpretation
DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823–834.
Summary
Objective
To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute ...Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction.
Methods
The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed.
Results
Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio OR = 0.84, 95% confidence interval CI = 0.77‐0.93 and OR = 1.34, 95% CI = 1.05‐1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06‐1.25).
Significance
Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.
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