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BackgroundTenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke (AIS). Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) for patients with AIS in China.MethodsThis multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis. The safety outcome were symptomatic intracranial haemorrhage (sICH) within 36 hours.ResultsBetween May 2018 and February 2020, 240 patients were randomly assigned to four group, 4 of whom did not receive study treatment. The intention-to-treat analysis included 236 patients. There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group (63.3%, 77.2%, 66.7% vs 62.7%). The number of sICH was 3 of 60 (5.0%) in the 0.1 mg/kg group, none in the 0.25 mg/kg group, 2 of 60 (3.3%) in the 0.32 mg/kg group and 1 (1.7%) of 59 in the rt-PA group. There were no significant between-group differences in severe adverse events.ConclusionsSimilar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset. The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations.Trial registration number NCT04676659.

In this trial involving 543 patients with stroke due to occlusion of medium or distal vessels, endovascular treatment within 24 hours after the onset of symptoms was not effective in improving functional outcome at 90 days.

Biomarkers are objective indicators used to assess normal or pathological processes, evaluate responses to treatment and predict outcomes. Many blood biomarkers already guide decision-making in clinical practice. In stroke, the number of candidate biomarkers is constantly increasing. These biomarkers include proteins, ribonucleic acids, lipids or metabolites. Although biomarkers have the potential to improve the diagnosis and the management of patients with stroke, there is currently no marker that has demonstrated sufficient sensitivity, specificity, rapidity, precision, and cost-effectiveness to be used in the routine management of stroke, thus highlighting the need for additional work. A better standardization of clinical, laboratory and statistical procedures between centers is indispensable to optimize biomarker performance. This review focuses on blood biomarkers that have shown promise for translation into clinical practice and describes some newly reported markers that could add to routine stroke care. Avenues for the discovery of new stroke biomarkers and future research are discussed. The description of the biomarkers is organized according to their expected application in clinical practice: diagnosis, treatment decision, and outcome prediction.

Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES. Such recovery is associated to quantitative signatures of functional neuroplasticity. BCI patients exhibit a significant functional recovery after the intervention, which remains 6–12 months after the end of therapy. Electroencephalography analysis pinpoints significant differences in favor of the BCI group, mainly consisting in an increase in functional connectivity between motor areas in the affected hemisphere. This increase is significantly correlated with functional improvement. Results illustrate how a BCI–FES therapy can drive significant functional recovery and purposeful plasticity thanks to contingent activation of body natural efferent and afferent pathways. Brain-computer interface (BCI) can improve motor skills on stroke patients. This study shows that BCI-controlled neuromuscular electrical stimulation therapy can cause cortical reorganization due to activation of efferent and afferent pathways, and this effect can be long lasting in a brain region specific manner.

The systemic inflammation score (SIS) has been utilised as a representative biomarker for evaluating nutritional and inflammation status. However, the predictive value of SIS has not been reported in patients with acute ischemic stroke (AIS). We aimed to evaluate whether SIS is associated with prognosis in stroke. A total of 4801 patients with AIS were included in the study. The primary outcome was a modified Rankin Scale score>2 at the 3-month follow-up. A total of 4801 patients were randomly allocated into training (n=3361) and validation cohorts (n=1440) at a ratio of 7:3. Model performance was validated using the receiver operating characteristic (ROC) curve and calibration curve. Additionally, a comparison was made between the nomogram and the THRIVE score in regards to their respective predictive capabilities. Overall, 1091(32.5%) patients in the training cohort and 446 (31.0%) patients in the validation cohort experienced an unfavorable outcome. The multivariate logistic regression analysis revealed that a high SIS, age, NIHSS, diabetes and prior stroke were associated with unfavorable outcome. Our nomogram was developed based on the variables mentioned above. The area under the curve (AUC) of the training set and the validation set are 0.702 and 0.708, respectively, indicating that the model has modest agreement and discrimination. The results of AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) showed that nomogram had significantly higher predictive value than THRIVE scores (all P<0.001). However, unlike the THRIVE publication, all patients who had undergone intravenous thrombolysis or endovascular thrombectomy therapy were excluded in our study. In consequence, our derived THRIVE scores cannot be compared to those in the original THRIVE study. The SIS exhibits potential as a simple prognostic biomarker, and the nomogram, which utilizes the SIS, may serve as a valuable tool for clinicians in the early identification of patients at heightened risk for unfavorable outcomes. •The predictive value of systemic inflammation score (SIS) has not been reported in patients with acute ischemic stroke (AIS).•We aimed to prospectively investigate whether SIS is associated with the prognosis of ischemic stroke patients in a large-scale cohort study.•The nomogram based on SIS may serve as a valuable tool for clinicians identifying patients at heightened risk for unfavorable outcomes.

Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. 237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients.

Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AFrandomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4–14·5, p=0·002; number needed to screen 11). Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). Boehringer Ingelheim.

This trial assessed the value of brain imaging to guide treatment for stroke. Clinical outcomes with embolectomy were not superior to those with standard care in all patients or in the subgroup identified by brain imaging as most likely to benefit from embolectomy. Multiple randomized, controlled trials have shown the efficacy of the use of intravenous tissue plasminogen activator (t-PA), administered up to 4.5 hours after the onset of symptoms of acute ischemic stroke. 1 , 2 However, the global effect of this therapy has been limited, largely because of the narrow time window available for treatment and the risk of symptomatic intracerebral hemorrhage. Although endovascular approaches, including thrombectomy devices, have been shown to achieve greater rates of recanalization than the use of intravenous t-PA, no randomized, controlled trial has been completed comparing clinical outcomes versus standard medical care. Moreover, the potential to benefit from . . .

Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, ie, ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care.

In patients with stroke and patent large and medium-sized cerebral vessels, the glycoprotein IIb/IIIa receptor inhibitor tirofiban resulted in a greater likelihood of an excellent outcome than low-dose aspirin.