Clinical evidence requirements for high-risk endovascular stroke devices in Europe remain heterogeneous, reflecting limited indication-specific methodological guidance under the European Medical Device Regulation (MDR) and resulting in uncertainty regarding the design and appraisal of clinical investigations across jurisdictions. We combined a systematic review of clinical studies evaluating endovascular stroke devices with a European multisociety expert consensus using a modified Delphi process. Eighteen experts representing the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Stroke Organisation (ESO), and the European Society of Neuroradiology (ESNR) participated in three Delphi rounds to formulate clinically grounded methodological recommendations for regulatory device evaluation. Prospective observational studies, including externally controlled comparative designs and single-arm studies based on performance benchmarks or precision-based estimation, were considered appropriate for most regulatory and clinical scenarios. For conceptually novel devices, no consensus was reached on a single optimal study design, leaving room for both randomized trials and observational approaches depending on the level of uncertainty. Consensus was achieved on key elements of study design, including multicenter structure, center and operator requirements, independent monitoring, imaging core-laboratory adjudication, endpoint selection, and data transparency. Functional independence at 90 days, successful reperfusion, and symptomatic intracranial hemorrhage were identified as core outcome domains. This clinician-driven consensus provides practical, indication-specific methodological recommendations for the design and conduct of regulatory studies evaluating single-use endovascular stroke devices. It complements existing frameworks, including CORE-MD and ISO-based guidance, by translating general principles into clinically applicable standards for neurointerventional research and regulatory trial design.
The Stroke Action Plan for Europe (SAP-E) calls for equitable access to evidence-based acute stroke care, yet within-country variation remains underexplored. We mapped reperfusion capabilities, imaging resources and organisational structures across all Norwegian hospitals providing acute stroke care. In 2024, we conducted a cross-sectional survey of all 50 acute stroke hospitals. Data covered reperfusion protocols, advanced imaging availability and the organisational maturity of regional stroke networks. Hospitals were categorised by their most advanced routinely available strategy: intravenous thrombolysis (IVT) within 0-4.5 h (IVT ≤ 4.5 h); IVT in wake-up stroke; IVT in both wake-up stroke and the extended window or endovascular thrombectomy (EVT) capability. All hospitals providing local acute stroke treatment offered IVT ≤ 4.5 h, while 3 hospitals in South-Eastern Norway had a stroke unit but transferred all acute patients directly to a comprehensive stroke centre. Eleven hospitals (22%) provided IVT ≤ 4.5 h only, 8 (16%) implemented IVT for wake-up stroke and 28 (56%) offered IVT for both wake-up and extended-window thrombolysis. Eight hospitals (16%) were EVT-capable, unevenly distributed. CT perfusion (CTP) was available in 28 hospitals (56%), and acute MRI in 17 (34%). Regional stroke networks varied widely in structure and activity, from well-organised, funded systems to inactive or absent networks. Norway shows universal IVT access within 0-4.5 h but marked regional variation in advanced treatment, imaging and coordination. Strengthening and standardising regional stroke networks may be key to achieving SAP-E's vision of equitable, high-quality care.
Prehospital stroke scales are widely used to identify patients with suspected stroke. The scales have shown potential to identify suspected large-vessel occlusion (LVO) for direct-to-thrombectomy triage, yet it remains unclear which scales perform best, and whether performance varies by patient characteristics. In this retrospective diagnostic accuracy study, we analysed 1150 consecutive adults admitted under the stroke code protocol at a primary stroke centre (January 2015-December 2017). The cohort included ischaemic stroke, transient ischaemic attack, intracerebral haemorrhage and mimics. We evaluated 55 scale-threshold combinations (46 scales) for detection of computed tomography angiography (CTA)-confirmed LVO, quantified by area under the receiver operating characteristic curve (AUC), sensitivity, specificity and predictive values. In our study population, LVO prevalence was 13.5%. AUC ranged from 0.586 (Hemiplegia) to 0.855 (FAST-ED). No scale significantly outperformed the continuous National Institutes of Health Stroke Scale (NIHSS, AUC 0.851) after Bonferroni correction, and none achieved both sensitivity and specificity above 80%. Scales combining cortical and motor items outperformed purely motor-based instruments. Accuracy was comparable between sexes but higher for left-hemispheric strokes (mean AUC: 0.82 vs 0.76) and patients aged ≥60 years (0.82 vs 0.77). None of the prehospital stroke scales were accurate enough to reliably detect LVO. Performance varied with stroke laterality, patient age and stroke severity-approaching chance levels at the extremes of severity and showing a consistent hemispheric bias. This highlights fundamental limitations of using clinical scales alone to detect LVO in real-world stroke code populations. Registration:  ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05378490, NCT05378490.
Cardiac disease is a leading cause of arterial ischaemic stroke (AIS) in children, yet data on paediatric cardioembolic stroke remain limited. This study investigated the incidence rate, underlying cardiac diseases and outcome of paediatric cardioembolic stroke in Denmark. In a nationwide registry, we identified all children with a stroke or stroke-related diagnosis (2013-2020). Arterial ischaemic stroke events were confirmed by medical record review and classified using the Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria as definite cardioembolic, probable cardioembolic or non-cardioembolic. Neuroimaging and neurological outcomes were extracted from medical records. Follow-up time was 2 years. Cardioembolic stroke was identified in 31 (24.6%) of 126 children with AIS, corresponding to an incidence rate of 0.28 (95% CI, 0.20-0.40) per 100,000 person-years. Congenital heart diseases were the most common underlying conditions (n = 26, 83.9%). Among children undergoing angiography, LVOs were present in 41.2% of the cardioembolic group and in 18.5% of the non-cardioembolic group (P-value .060). The frequency of neurological impairments was similar between cardioembolic and non-cardioembolic AIS (48.4% vs 43.6%, P = .681). When limiting analysis to definite cardioembolic stroke, neurological impairment was more common in the cardioembolic than the non-cardioembolic group (73.3% vs 43.6%, P = .050), though this association was non-significant after adjusting for stroke severity. Cardioembolic stroke accounted for nearly one-quarter of paediatric AIS events. While clinical outcomes were similar between cardioembolic and non-cardioembolic AIS, definite cardioembolic stroke was associated with a higher risk of incomplete neurological recovery, highlighting the need for improved preventive strategies.
Despite remarkable advances in stroke management, there is a continued lack of evidence to guide care for the 1 in 3 stroke patients living with disability or dementia (PLWD). To help inform best practices, this study sought to understand how physicians approach the complex issue of determining goals of care for PLWD and what challenges they encounter. In a mixed-methods investigation, we invited physicians involved in stroke care to participate in semistructured interviews and an online survey, enquiring into perspectives on stroke management in PLWD. Interviews were analyzed using an interpretive grounded theory approach. Qualitative findings were triangulated with results from a descriptive analysis of survey items. Of 82 approached physicians, 30 participated in interviews (43% from North America, 77% with ≥10 years of experience; 60% neurologists); of 200 consenting to the survey, 132 completed it (37% from North America, 51% with ≥10 years of experience, 56% neurologists). For both prestroke disability and dementia, survey respondents most frequently indicated severity of the prior condition (87% [95% CI, 80%-91%] and 89% [95% CI, 82%-93%]) and quality of life (88% [95% CI, 82%-93%] and 87% [95% CI, 80%-91%]) as either very or extremely important in decision-making. However, interviewed physicians emphasized uncertainty in evaluating these factors and forming perceptions of patient prognosis and treatment appropriateness. This was attributed to limited reliable information regarding patients' prior well-being and wishes, and paucity of PLWD-specific evidence to guide stroke management. While these ambiguous circumstances appeared to warrant a highly individualized approach to care, physicians also recognized the consequent high risk of biases affecting equity. Physicians encounter profound, multifaceted uncertainty in determining goals of care for PLWD, which may contribute to adverse variability in stroke management. This uncertainty may be eased by routinely documenting patients' baseline well-being and advance healthcare directives in clinical practice and promoting inclusion of PLWD in stroke research, in both contexts, considering patient and family perspectives on quality of life and favorable outcomes.
Stroke remains a leading cause of death and disability across the Americas, disproportionately affecting low- and middle-income countries. According to the 2023 Global Burden of Disease (GBD) Study, the Americas recorded approximately 1.2 million incident strokes and 15.7 million prevalent cases. This narrative review synthesizes epidemiological evidence on stroke trends in the Americas, with emphasis on disparities in healthcare access. We integrated estimates from the GBD, peer-reviewed studies and national surveillance systems. Although age-standardized stroke rates declined after 1990, recent analyses demonstrate a concerning resurgence, particularly among younger adults. Stroke incidence, prevalence, and disability burden vary widely across countries. Latin America and the Caribbean show higher incidence but lower prevalence than high-income settings, reflecting limited access to acute care and higher case fatality. Socioeconomic and racial inequities drive delayed treatment and poorer functional outcomes. Over 75% of stroke burden is attributable to modifiable risk factors. Urgent system-level action is needed. O acidente vascular cerebral (AVC) permanece como uma das principais causas de morte e incapacidade nas Américas, afetando de forma desproporcional os países de baixa e média renda. De acordo com o estudo Global Burden of Disease (GBD) 2023, as Américas registraram aproximadamente 1.2 milhão de casos incidentes de AVC e 15.7 milhões de casos prevalentes. Esta revisão narrativa sintetiza evidências epidemiológicas sobre as tendências do AVC nas Américas, com ênfase nas desigualdades no acesso à assistência em saúde. Foram integradas estimativas do GBD, estudos revisados por pares e sistemas nacionais de vigilância. Embora as taxas de AVC padronizadas por idade tenham diminuído após 1990, análises recentes demonstram uma preocupante retomada do aumento, particularmente entre adultos mais jovens. A incidência, prevalência e carga de incapacidade por AVC variam amplamente entre os países. A América Latina e o Caribe apresentam maior incidência, porém menor prevalência em comparação com países de alta renda, refletindo acesso limitado ao cuidado agudo e maior letalidade. Desigualdades socioeconômicas e raciais contribuem para atrasos no tratamento e piores desfechos funcionais. Mais de 75% da carga de AVC é atribuível a fatores de risco modificáveis, ressaltando a necessidade urgente de ações em nível de sistema de saúde. El accidente cerebrovascular (ictus) sigue siendo una de las principales causas de mortalidad y discapacidad en las Américas, afectando de manera desproporcionada a los países de ingresos bajos y medianos. Según el estudio Global Burden of Disease (GBD) 2023, las Américas registraron aproximadamente 1.2 millones de casos incidentes de ictus y 15.7 millones de casos prevalentes. Esta revisión narrativa sintetiza la evidencia epidemiológica sobre las tendencias del ictus en las Américas, con énfasis en las desigualdades en el acceso a la atención sanitaria. Se integraron estimaciones del GBD, estudios revisados por pares y sistemas nacionales de vigilancia. Aunque las tasas de ictus ajustadas por edad disminuyeron después de 1990, análisis recientes muestran una preocupante reaparición del aumento, particularmente entre adultos más jóvenes. La incidencia, la prevalencia y la carga de discapacidad por ictus varían ampliamente entre los países. América Latina y el Caribe presentan una mayor incidencia, pero una menor prevalencia en comparación con los países de altos ingresos, lo que refleja un acceso limitado a la atención aguda y una mayor letalidad. Las desigualdades socioeconómicas y raciales contribuyen a retrasos en el tratamiento y a peores resultados funcionales. Más del 75% de la carga del ictus es atribuible a factores de riesgo modificables, lo que subraya la necesidad urgente de acciones a nivel de los sistemas de salud.
Moyamoya angiopathy (MMA) is a cerebrovascular disease treated by surgical revascularization. This study aimed to present long-term outcomes of European MMA patients after surgical revascularization. MMA patients treated surgically between 1998 to 2023 were included. Follow-up comprised clinical and radiological examinations and electronic questionnaires. Patient data were analyzed retrospectively, and logistic regressions were performed to identify predictors of unfavorable outcomes. A total of 276 patients with 428 surgically treated hemispheres were included. The mean age was 35.0 ± 17.2 years, including 192 women and 84 men, predominantly of Caucasian ethnicity (88.0%). Ischemia (82.2%) and hemorrhage (10.1%) were the most common symptoms at onset. Most adults (80.9%) were treated with combined bypass surgery via mini-craniotomy. Within 30 days, complications occurred in 6.3% of surgeries, and the perioperative stroke risk was 2.6%. A total of 148 patients underwent in-house follow-up. No mRS scores ≥ 5 were observed, with 86.3% of patients achieving a score of 0-2, alongside a bypass patency rate of 95.7% and a stroke risk of 0.3% per patient-year. Preoperative stroke and silent ischemic MRI lesions were identified as predictors of an unfavorable outcome. Additionally, 201 patients were followed up electronically. No mRS scores ≥ 5 were observed, with 87.9% of patients achieving a score of 0-2. Moreover, 90.7% were independent in daily life, but only 50.5% returned to work or school. Combined bypass surgery yielded favorable outcomes with low complication and stroke rates. Patients with preoperative stroke require closer follow-up, and individualized strategies are needed to address persistent functional impairments.
Guidelines recommend cognitive screening post-stroke, but there is no consensus on approach. Given the dynamic nature of cognition following stroke, acute screening should both detect prevalent issues (diagnosis) and predict persisting problems (prognosis). We describe the diagnostic and prognostic utility of brief cognitive screening tools. Patients were screened on admission with stroke using 12 modified screening tests: 10 and 4 question Abbreviated Mental Test, Cog-4, Clock Drawing test (CDT), Cognitive Impairment Test, informal bedside assessment, General Practitioner Assessment of Cognition, Minicog, Short Form Montreal Cognitive Assessment, Six-Item Screener (SIS), Harmonised Vascular Cognitive Impairment battery and 4-A's Test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were calculated against a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition adjudicated reference standard of neurocognitive disorders. Test accuracy was compared using area under the receiver operator characteristic curves. Of 335 patients, 54 (16.1%) had pre-stroke neurocognitive disorder, 79 (23.6%) had 18-month neurocognitive disorder. Ten of 12 screening tests were more specific than sensitive. Informal bedside assessment had highest specificity (96%), but low sensitivity (9%); CDT had highest sensitivity (80%) but low specificity (33%). Negative predictive value ranged from 77% to 87%, PPV ranged from 27% to 54%. Area under the receiver operator characteristic curve ranged 0.53 (informal bedside assessment) to 0.69 (SIS). In the acute setting, where the intention of screening is often to triage those who need further assessment, the pattern of high specificity at the expense of sensitivity is the opposite of what is desired. Brief cognitive screening tools, used in isolation, may not be suitable for assessment in acute stroke settings.
Assessment of mild acute ischemic stroke (mAIS) can be difficult, especially in regions where access to neuroimaging is limited. Integrating routine blood analyses with wearable gait assessments may aid in the identification of mAIS and estimation of functional outcomes. In this pilot study, we focus on identifying candidate gait and blood analytes associated with stroke status and functional outcomes in mAIS. Video, smartphone, and blood data were collected from 22 mAIS patients and nine healthy controls. Ridge-penalized logistic regression nomograms were developed; one to estimate the stroke status using gait, and a second one to estimate walking speed of patients using blood analytes. Our gait-based nomogram identified mAIS with an area under the curve (AUC) of 0.878, while blood-based nomogram estimated walking speed with an AUC of 0.906 (both optimism-corrected). Identified gait features for stroke status included lower xgyr_energy, xgyr_max, xgyr_std, zgyr_energy and zacc_rms, and higher zgyr_iqr, while higher age, blood urea nitrogen (BUN), and lower estimated glomerular filtration rate (eGFR) and mean corpuscular hemoglobin concentration (MCHC) were associated with slower walking. We show the feasibility of integrating gait statistics with blood analytes to identify mAIS and estimate walking speed. The nomograms showed strong discrimination and calibration within our small cohort. These findings point to the potential of multimodal signal-based features in stroke detection and rehabilitation planning, particularly in low-resource settings.
To explore the association between an optimised emergency procedure combined with structured health education and anxiety, depression and treatment outcomes in patients with acute ischaemic stroke (AIS). We conducted a retrospective cohort study of 114 AIS patients admitted to our stroke centre between January and December 2023. On the basis of the admission timeframe, patients were divided into a conventional care group (n = 57, January to June 2023, routine care) and a comprehensive nursing group (n = 57, July to December 2023, optimised integrated care). Emergency nursing outcomes were assessed after stabilisation and before ward transfer. Neurological recovery was assessed with the European Stroke Scale (ESS); anxiety and depression were assessed with the Generalized Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ-9) as primary psychological indicators. Process times and nursing satisfaction were also evaluated. Data analysis was conducted using SPSS 27.0. Normality was verified using the Shapiro-Wilk test. Normally distributed data were expressed as mean ± standard deviation and analysed using an independent samples t-test, whereas non-normal data were expressed as median (interquartile range) and analysed using the Mann-Whitney U test. Categorical data were analysed using chi-square test. Multivariate linear and logistic regression were used to analyse indicators such as neurological function and nursing satisfaction, adjusting for confounding factors. A p-value < 0.05 was considered statistically significant. Compared with the conventional care group, the waiting time, diagnosis time, emergency room waiting time and recanalisation time of patients in the comprehensive nursing group were significantly shortened (p < 0.05). The degree of improvement in ESS (∆ESS) in the comprehensive nursing group was significantly higher, and the reductions in GAD-7 and PHQ-9 scores were also significantly greater (p < 0.05). Patient and family satisfaction in the comprehensive nursing group were significantly higher than those in the conventional care group (p < 0.05). Through multivariate linear regression analysis, with baseline National Institutes of Health Stroke Scale (NIHSS) score, time from onset to visit, hypertension and diabetes as adjustment factors, allocation to the comprehensive nursing group was still significantly correlated with ∆ESS (β [95% confidence interval (CI)] = 8.15 [5.72 to 10.58], p < 0.001), ∆GAD-7 (β [95% CI] = -2.18 [-2.92 to -1.44], p < 0.001), and ∆PHQ-9 (β [95% CI] = -2.65 [-3.32 to -1.98], p < 0.001). The results of multivariate logistic regression analysis showed that, after adjusting for the above confounding factors, inclusion in the comprehensive nursing group was independently associated with a significantly higher likelihood of obtaining a satisfactory nursing evaluation (adjusted OR = 8.915, 95% CI: 2.453 to 32.468, p = 0.001). The integrated model is associated with shorter treatment times, better neurological recovery, reduced anxiety and depression and higher satisfaction in AIS patients, providing preliminary evidence for a patientcentred comprehensive emergency care model.
ObjectiveTo assess the causal effects of specific eating habits on ischemic stroke risk and functional outcomes using Mendelian randomization.MethodsThis two-sample Mendelian randomization study used genetic variants associated with 32 eating habits as instrumental variables. Summary-level data were obtained from large-scale genome-wide association studies of individuals of European ancestry. The primary analysis used the inverse-variance weighted method, supplemented by sensitivity analyses to assess pleiotropy and multivariable Mendelian randomization to evaluate mediation via lipids and blood pressure.ResultsAfter multiple-testing correction, genetically predicted higher intake of cheese (odds ratio = 0.70, 95% confidence interval: 0.57-0.86), dried fruit (odds ratio = 0.57, 95% confidence interval: 0.41-0.80), and muesli (odds ratio = 0.20, 95% confidence interval: 0.07-0.54) showed potential protective associations with ischemic stroke risk. Sensitivity analyses supported the robustness of the findings, and multivariable Mendelian randomization indicated that the effects of cheese and muesli remained significant after adjustment for cardiovascular risk factors. No causal associations were observed for post-stroke recovery.ConclusionThis study provides genetically derived causal evidence suggesting that higher consumption of cheese, dried fruit, and muesli may reduce the risk of ischemic stroke. Further studies are warranted to validate these food-specific dietary recommendations.
Glucagon-like peptide-1 receptor agonists have been shown to have neuroprotective effects in metabolic diseases, but their application in neurodegenerative diseases (stroke and Parkinson's disease) has not been adequately studied. To assess the neuroprotective effects of GLP-1 receptor agonists in experimental stroke and Parkinson's disease models, in terms of mechanisms, properties of intervention, and major neurological outcomes. A systematic review was performed according to PRISMA. Four databases Cochrane CENTRAL, PubMed, Web of Science and Scopus were searched and 1643 records identified and 13 experimental animal studies were included. The SYRCLE tool was used to extract data and assess the risk of bias. 13 experimental studies published in 2013-2026 were included, which involved models of stroke and Parkinson disease. The MCAO models were the main models used in stroke studies, with a significant decrease in infarct volume, such as 15.4 % ± 1.3 % (liraglutide) and 40 % reduction with linagliptin. The score in neurological deficit was also found to improve (1.1 ± 0.14; P < 0.05) and the size of the infarct in treated groups had also reduced (36.5 % to 8.2 %; P = 0.001). The research on Parkinson disease showed that there was a notable improvement in motor functions (P < 0.001), preservation of dopaminergic neurons, and a decrease in the aggregation of α-synuclein. GLP-1 agonists decreased neuroinflammatory (TNF-α, IL-1b, IL-6), oxidative (ROS, 4-HNE), and apoptotic (increased Bcl-2, decreased Bax) markers. The treatment was between 24 h and 20 weeks, and the doses also differed among the agents. The overall quality of risk of bias assessment was moderate, with four studies having a high risk because of small sample size and inadequate reporting on the randomization and blinding. GLP-1 receptor agonists have powerful neuroprotective activity in preclinical models of stroke and Parkinson disease, which is multi-targeted. To ensure translational potential and to maximize therapeutic strategies, standardized studies and clinical trials are needed.
The optimal imaging modality for selecting stroke patients for revascularisation in the extended window remains uncertain. The VESTA study compared simple (non-contrast CT + CTA) vs advanced imaging (including perfusion) in the extended window in terms of clinical outcomes, mortality and safety. This multicentre cohort study included 1262 stroke patients (last seen well 6-24 h, NIHSS ≥ 6) from the Catalan Stroke Registry (2019-2021). A central core lab re-evaluated images, and blinded investigators assessed 90-day functional outcomes. Inverse probability weighting (IPW) and multivariable methods were applied. Median age was 76 years, NIHSS 12 and 48% were women. Simple imaging was used in 44% (n = 550), advanced in 56% (n = 712). Simple imaging had higher rates of no arterial occlusion (49% vs 37%, P = .006) and slightly lower endovascular treatment rates (36% vs 40%, P = .117). Time metrics were similar. In the IPW analysis, (advanced imaging as reference), simple imaging showed numerically worse point estimates across all outcomes, although most differences did not reach statistical significance: a worse mRS shift (adjusted odds ratio [aOR] 1.17 [95% CI, 0.96-1.43]; P = .11), a lower good functional outcome (mRS 0-2; aOR 0.83 [0.66-1.06]; P = .13), a higher mortality (aOR 1.20 [0.91-1.58]; P = .20), more frequent sICH (aOR 1.25 [0.61, 2.57]; P = .55) and a higher risk of any ICH (aOR 1.57 [1.00-2.47]; P = .05). In moderate-to-severe stroke (NIHSS ≥ 6) within 6-24 h, simple imaging did not show a statistically significant difference vs advanced imaging for guiding stroke treatment. However, advanced imaging may improve patient selection for reperfusion and reduce haemorrhagic risk. This study was registered at ClinicalTrials.gov under NCT05299034.
Endothelial activation and stress index (EASIX) is a biomarker of endothelial dysfunction and has been validated previously as a prognostic score for mortality in various diseases, including oncologic diseases, sepsis, and cardiac disease. Since endothelial dysfunction is an established mediator of adverse outcomes in acute ischemic stroke, this study investigates the prognostic value of EASIX for risk of mortality in these patients. We analyzed data from the Heidelberg (n = 4,188) and Vienna (n = 2,273) prospective acute ischemic stroke registries. EASIX was calculated as creatinine [mg/dL] × LDH [U/L] / platelet count [109/L]. An EASIX cut-off was established using maximal Youden index. Validation was performed using Brier score and C-statistics. Higher EASIX was associated with higher risk of mortality in the training cohort in a multivariable Cox regression (HR of all-cause mortality per log2 increase: 1.20 (95% CI 1.12-1.28), p < 0.001). An optimal EASIX cut-off value of 1.211 was identified in the derivation cohort. In the independent validation cohort, this cut-off was associated with risk of 3-month mortality in a multivariable binary logistic regression model (OR 1.86 (1.28-2.70), p < 0.01). Brier score and C-statistics validated the superior predictive performance of EASIX in the multivariable model. EASIX predicts mortality in acute ischemic stroke patients and retained prognostic validity across two heterogeneous European cohorts. Incorporation of EASIX improved risk stratification beyond established clinical scores. EASIX may serve as a useful tool for risk stratification and outcome prediction in acute ischemic stroke patients.
Home-based rehabilitation after stroke is increasingly important, as pressure on hospital services rise and recovery occurs mostly at home. Enriching the home (Environmental Enrichment, EE) represents a potential strategy to support rehabilitation by providing continuous task- and context-specific stimulation that promotes functional recovery through frequent and exploratory use of the affected arm. Exploratory behaviour - self-initiated, varied and adaptive movements - is an important driver of motor learning and neuroplasticity. While strong evidence from animal research demonstrates the benefits of EE for functional recovery, translation to human home-based rehabilitation remains limited. This study will investigate the feasibility of the Pedagogy and Enriched Environment for Rehabilitation in the HOME after stroke (PEER-HOMEcare) intervention. PEER-HOMEcare translates EE by introducing meaningful, targeted and progressive home modifications to promote exploratory use of the affected arm during daily activities. In this prospective, single group, experimental study, 45 stroke survivors (≥ 18 years), within 6 months post-stroke across Norway, Sweden and Latvia will participate. Wearable sensors will be used to capture exploratory behaviour and activity patterns, giving objective insights to inform progressive modifications to the home. Primary outcomes of feasibility and acceptability will be assessed through questionnaires, logs and interviews. Intervention fidelity, participant adherence and adverse events will be evaluated. Secondary outcomes include changes in arm function, self-perceived activities of daily living and psychosocial outcomes. This study will provide important knowledge about the feasibility of an innovative EE approach for home-based rehabilitation, informing a future trial evaluating its clinical effectiveness. Trial registration in https://www.ClinicalTrials.gov on 06-04-2026, NCT07517120.
Magnetic resonance imaging (MRI) is critical for acute stroke triage, but it is time-consuming and often requires contrast injection for perfusion imaging. This study aimed to synthesize T-map perfusion maps from routinely available, noncontrast diffusion-weighted imaging and fluid-attenuated inversion recovery using deep generative models. We hypothesized that relevant perfusion information could be inferred from these modalities to streamline imaging and reduce reliance on dynamic susceptibility contrast perfusion. Acute magnetic resonance imaging data from 355 patients with anterior circulation stroke, including dynamic susceptibility contrast perfusion, were retrospectively collected from 2 European centers (Heidelberg: 2010-2018; Bordeaux: 2021-2022). Six versions of a denoising diffusion probabilistic model and a generative adversarial network architecture were trained to generate synthetic time-to-maximum (T-max) perfusion maps from diffusion-weighted imaging, fluid-attenuated inversion recovery, and infarct core mask as inputs. Performance was assessed by comparing synthetic and ground-truth T-max maps using image similarity metrics. Regions with T-max >6 s were compared using Dice coefficients, and mismatch volume distributions were analyzed. An ablation study quantified the contribution of each input. The best performance was achieved by a denoising diffusion probabilistic model with a 2.5D architecture using diffusion-weighted imaging, fluid-attenuated inversion recovery, infarct core mask, and a perfusion-weighted loss function. It produced synthetic perfusion T-max maps with high similarity to ground truth under 110 s. The model showed strong spatial overlap for T-max> 6 s regions in internal validation (average Dice, 0.82; SD, 0.08) and external validation (average Dice, 0.59; SD, 0.13), respectively. Synthetic maps closely matched ground truth mismatch distributions, capturing key perfusion patterns. The infarct core mask played a critical role in model performance, alongside diffusion-weighted imaging and fluid-attenuated inversion recovery inputs. We propose a noninvasive, scalable framework to generate synthetic T-max perfusion maps from noncontrast magnetic resonance imaging. This approach could expand access to perfusion data in acute stroke, shorten imaging protocols, and accelerate treatment decisions by eliminating the need for contrast-enhanced acquisition.
Traditional endpoints in acute ischaemic stroke trials, most commonly the mRS, incompletely capture the full spectrum of patient outcomes. The win ratio (WR) is a hierarchically structured composite outcome measure that prioritises endpoints according to clinical importance. In this study, we applied win statistics to investigate which components drive the overall treatment effect. Of 253 patients in the TENSION (Efficacy and safety of ThrombEctomy iN Stroke with extended leSION and extended time window) trial, 125 were randomised to EVT + BMT and 128 to BMT alone. Endpoints were ranked hierarchically: (1) time to death, (2) mRS at 12 months, (3) occurrence of any serious adverse event and (4) EuroQOL 5-dimension scores at 12 months. Outcomes were analysed using win statistics. The overall WR was 1.61 (95% CI, 1.19-2.18; P = .002), indicating a relative frequency of wins for EVT + BMT of approximately 60% among untied pairwise comparisons. The win difference was 22.8% (95% CI, 8.3%-36.3%; P = .002), of which 15.7% were attributable to survival. Win ratios were consistent across prespecified subgroups, including both sexes, age ≤ 80 years, baseline mRS 0-1, conscious patients, ASPECTS 5 and M1 occlusions. The WR provides an informative complement to conventional mRS-based analyses in acute ischaemic stroke trials. Our hierarchical composite outcome analysis demonstrated how ordering of hierarchical components affects the resulting estimates, with the predominant treatment effect in TENSION being driven by improved survival. These findings support the complementary use of hierarchical composite outcomes in future neurointerventional trials.
Clopidogrel therapy is recommended to prevent recurrent ischemic stroke. However, clopidogrel resistance exists. This study examines which enzymes are involved in clopidogrel resistance. The study group includes 402 neurology patients who had experienced a recurrent ischemic stroke while receiving clopidogrel monotherapy. Patients were genotyped for CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5, CYP1A2, ABCB1 and CES1A1. Phenotype frequencies were compared with those of a Global(G), European(E) and a local patient control(C) group. Only for ABCB1 a significant difference in phenotype distribution was seen (pG = 0.003, pE = <0.001, pC = 0.019). In patient with ABCB1 rapid efflux activity (3435TT), no other enzyme was significantly associated. In patients with ABCB1 normal efflux activity (3435CT/CC), CYP2C19 intermediate and poor metabolism were significantly associated (pE = <0.001, pG = <0.001, pC = 0.002). In patients with normal CYP2C19 metabolism, CYP2C9 intermediate and poor metabolism were significantly associated (pG = <0.001, pE = <0.001, pC = <0.001). Besides CYP2C19 clinical guidelines, also for ABCB1 and CYP2C9 guidelines are needed to prevent clopidogrel resistance.
This post-hoc subanalysis of the TENSION trial evaluated the association between anesthesia strategy and neurological outcomes in patients with large-core infarcts undergoing mechanical thrombectomy (MT). We analyzed patients from the interventional arm of the TENSION trial who underwent MT under general anesthesia (GA) or conscious sedation (CS). Anesthesia strategy was not prespecified and was selected by the local stroke team. Key outcomes included early neurological improvement (ENI) or deterioration (END), modified Rankin Scale (mRS) at 90 days, procedural metrics, and safety outcomes. Multivariable logistic regression was performed to assess the independent association between anesthesia strategy and ENI, END, and favorable functional outcome, defined as mRS 0-3 at 90 days. Sensitivity analyses were conducted in patients with successful reperfusion. A total of 117 patients were included, of whom 50 were treated under GA and 67 under CS. No significant differences were observed between GA and CS for ENI (46.0% vs. 62.7%, p = 0.09) or END (56.0% vs. 46.3%, p = 0.30) at 24 h. Likewise, 90-day functional outcome did not differ significantly between groups, with mRS 0-3 achieved in 24.0% of GA patients and 36.0% of CS patients (p = 0.057). In adjusted analyses, anesthesia strategy was not independently associated with ENI, END, or mRS 0-3 at 90 days. Reperfusion success, first-pass recanalization, and safety outcomes were similar between groups. In the sensitivity analysis restricted to successfully reperfused patients, total procedure time was shorter in the CS group, but neurological and functional outcomes remained similar. In this post-hoc subanalysis of patients with large-core infarcts undergoing MT, anesthesia strategy was not independently associated with early neurological or 90-day functional outcomes. GA and CS were associated with comparable procedural success and safety. Given the non-randomized design, limited sample size, and potential for residual confounding, further studies are needed to clarify optimal anesthesia selection in large-core stroke patients undergoing MT.
Adaptive servo-ventilation (ASV) effectively treats central sleep apnea (CSA), with or without coexisting obstructive sleep apnea (CSA-OSA). However, this is a diverse patient group, and the characteristics of patients who are most likely to benefit from ASV therapy, outside of traditional etiology-based subgroups, are unknown. To identify clusters of ASV-treated patients based on anthropometric data and comorbidities, and to evaluate the differential response to ASV in these patient clusters. This analysis used data from the READ-ASV registry, which enrolled adults with CSA prescribed ASV from September 2017-March 2021. Evaluations included the Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Pittsburg Sleep Quality Index, EuroQol-5-dimension, and sleep study data. Latent class analysis was used to identify patient clusters based on baseline anthropometric data and comorbidities. Of 812 patients, 421 (52%) were in Cluster (C) 1 (older, high rate of cardiovascular comorbidities [including stroke], high body mass index [BMI]), 239 (29%) were in C2 (elderly/middle-aged, average-low cardiovascular comorbidity rate, high stroke rate, lower BMI, low diabetes rate), and 152 (19%) were in Cluster 3 (younger, low cardiovascular comorbidity rate, higher BMI, high depression rate). Patients from C3 versus C1/C2 had the highest apnea-hypopnea index at baseline (55 vs. 48/39.5 events/h), were the most symptomatic, had the worst quality of life (QoL), and had the greatest symptomatic and QoL improvement on ASV. They remained the most symptomatic cluster after treatment. The identification of subgroups of ASV users with differing responses to therapy and residual symptom burden could facilitate a more personalized approach to ASV prescription and therapy management. https://www. gov; NCT03032029.