European Stroke Journal最新文献

Rationale: Whether endovascular therapy (EVT) in addition to best medical treatment (BMT) in people with acute ischemic stroke (AIS) due to a medium distal vessel occlusion (MDVO) is beneficial remains unclear.

Aim: To determine if people experiencing an AIS due to an isolated MDVO (defined as the co- or non-dominant M2 segment, the M3 or M4 segment of the middle cerebral artery, the A1, A2, or A3 segment of the anterior cerebral artery or the P1, P2 or P3 segment of the posterior cerebral artery) will have superior outcome if treated with EVT in addition to BMT compared to BMT alone.

Sample size: To randomize 526 participants 1:1 to EVT plus BMT or BMT alone.

Methods and design: A multicentre, international, prospective, randomized, open-label, blinded-endpoint (PROBE) superiority trial.

Outcomes: The primary efficacy endpoint is the distribution of disability levels on the modified Rankin Scale at 90 days. Secondary clinical efficacy outcomes include normalized change in National Institutes of Health Stroke Scale score from baseline to day 1, cognitive outcome at 90 days, and health-related quality of life at 90 days. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage within 24 h, and all-cause mortality up to 90 days. Secondary imaging outcomes include successful reperfusion at end of EVT procedure and recanalization of target artery at 24 h.

Discussion: DISTAL will inform physicians whether EVT in addition to BMT in people with AIS due to a MDVO is more efficacious than BMT alone.

Background and aims: Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores.

Methods: We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset).

Results: Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance.

Discussion: Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.

Introduction: High quality of early stroke care is essential for optimizing the chance of a good patient outcome. The quality of care may be monitored by process performance measures (PPMs) and previous studies have found an association between fulfilment of PPMs and short-term mortality. However, the association with long-term mortality remains to be determined. We aimed to evaluate the association between fulfilment of PPMs and long-term mortality for patients with acute stroke in Denmark.

Patients and methods: We used data from Danish health care registers between 2008 and 2020 to identify all patients admitted with incident stroke (haemorrhagic (ICH) or ischaemic stroke). The quality of early stroke care was assessed using 10 PPMs. Mortality was compared using Cox proportional hazard ratios, risk ratios computed using Poisson regression, and standardized relative survival.

Results: We included 102,742 patients; 9804 cases of ICH, 88,591 cases of ischaemic stroke, and 4347 cases of unspecified strokes. The cumulative 10-year mortality risk was 56.8%. Fulfilment of the individual PPMs was associated with adjusted hazard rate ratios of death between 0.76 and 0.96. Patients with 100% fulfilment of all PPMs had a lower 10-year post-stroke mortality (adjusted risk ratio 0.90) compared to the patients with 0%-49% fulfilment and a standardized relative survival of 81.3%, compared to the general population.

Conclusion: High quality of early stroke care was associated with lower long-term mortality following both ICH and ischaemic stroke, which emphasizes the importance of continued attention on the ability of stroke care providers to deliver high quality of early care.

Introduction: Malnutrition is common in stroke patients and has been associated with poor functional outcomes and increased mortality after stroke. Previous research on nutrition status and post-intracerebral hemorrhage (ICH) outcomes, however, is limited and conflicting.

Patients and methods: Monocenter study of patients with spontaneous deep or lobar ICH from a longitudinal cohort enrolling consecutive patients between 1994 and 2022. Nutrition status was assessed using admission body mass index (BMI), albumin, total bilirubin, cholesterol, c-reactive protein, hemoglobin a1c, high-density lipoprotein, hemoglobin, low-density lipoprotein, mean corpuscular volume, alanine transaminase, and triglycerides. Main outcome was favorable discharge outcome (mRS 0-2). Multivariable logistic regression was conducted with adjustment for baseline differences.

Results: Among 2170 patients, 1152 had deep and 1018 had lobar ICH. Overweight BMI was associated with higher odds of favorable discharge outcome in all (aOR = 3.01, 95% CI 1.59-5.69, p = 0.001) and lobar (aOR = 3.26, 95% CI 1.32-8.08, p = 0.011) ICH after adjustment for baseline differences. This association did not reach statistical significance in deep (aOR = 2.77, 95% CI 0.99-7.72, p = 0.052) ICH. No lab values were associated with functional outcome in all, deep, or lobar ICH after adjustment.

Discussion and conclusion: Overweight BMI was associated with favorable discharge status after ICH. These findings could inform future studies to determine whether overweight BMI has a protective effect in ICH patients.

Introduction: Formulating reliable prognosis for ischemic stroke patients remains a challenging task. We aimed to develop an artificial intelligence model able to formulate in the first 24 h after stroke an individualized prognosis in terms of NIHSS.

Patients and methods: Seven hundred ninety four acute ischemic stroke patients were divided into a training (597) and testing (197) cohort. Clinical and instrumental data were collected in the first 24 h. We evaluated the performance of four machine-learning models (Random Forest, K-Nearest Neighbors, Support Vector Machine, XGBoost) in predicting NIHSS at discharge both in terms of variation between discharge and admission (regressor approach) and in terms of severity class namely NIHSS 0-5, 6-10, 11-20, >20 (classifier approach). We used Shapley Additive exPlanations values to weight features impact on predictions.

Results: XGBoost emerged as the best performing model. The classifier and regressor approaches perform similarly in terms of accuracy (80% vs 75%) and f1-score (79% vs 77%) respectively. However, the regressor has higher precision (85% vs 68%) in predicting prognosis of very severe stroke patients (NIHSS > 20). NIHSS at admission and 24 hours, GCS at 24 hours, heart rate, acute ischemic lesion on CT-scan and TICI score were the most impacting features on the prediction.

Discussion: Our approach, which employs an artificial intelligence based-tool, inherently able to continuously learn and improve its performance, could improve care pathway and support stroke physicians in the communication with patients and caregivers.

Conclusion: XGBoost reliably predicts individualized outcome in terms of NIHSS at discharge in the first 24 hours after stroke.

Background and purpose: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs.

Methods: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD² score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment.

Results: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding.

Conclusions: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings.

Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions.

Results: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7).

Conclusion: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window.

Trial registration number: clinicaltrials.gov; Unique identifier: NCT04096248.

Rationale: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery.

Aim and hypothesis: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo.

Design: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial.

Participants: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living.

Intervention: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset.

Comparison: Matching placebo plus standardized rehabilitation.

Outcomes: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events.

Conclusion: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

Introduction: The aim of this study was to estimate societal costs during the first year after stroke by degree of functional disability.

Patients and methods: Descriptive study of the cumulative costs incurred during 1-year follow-up of a cohort of patients with stroke in Catalonia (Spain) participating in a multicentre, population-based, cluster-randomised trial (RACECAT). Patients were recruited between September 2017 and January 2019. Costs were collected for each patient from stroke onset to 1-year follow-up through hospital accounting records, electronic healthcare records and structured telephone-based interviews at 6 and 12-months follow-up. Disability was assessed using the 90-day modified Rankin Scale (mRS). Healthcare, community care, and patient/family costs were included. We used complete data from 567 eligible participants. Cost data were analysed using generalised linear models (GLMs) with gamma distributions and log link functions. For variables with >10% zero values, two-part models were applied. We performed sensitivity analyses modifying unit costs for patient/family costs.

Results: Of the 567 patients included, 53% had ischaemic large vessel oclusion (LVO) stroke, 24% intracranial haemorrhage and 23% ischaemic non-LVO stroke. Mean cost per patient during the first year after stroke was €29,673 ± 28,632, and increased with degree of disability (mRS 0-2: €18,568 ± 12,244; mRS 3: €38,214 ± 28,172; mRS 4-5: €52,859 ± 36,383). Healthcare costs represented the highest proportion of total costs (63%; €18,724/patient) across all disability levels, with index hospitalisation being the highest (€12,319 ± 17,675); however, community care and patient/family costs represented over 40% of total cost in patients with higher disability levels.

Discussion and conclusion: Our results are in line with other studies; the costs during the first year after stroke are high and increase with disability. These results are valuable for calculating the cost of severe stroke cases.